Pharmacogenetics Report
20250516113302
Date createdMay 16, 2025
Data Version2025-03-07-16-38

Sections

  1. Genotype Summary
  2. Prescribing Recommendations
  3. Allele Matching Details
  4. Disclaimers
Disclaimer: This report is only able to generate recommendations based on the information provided to the software. The gene and variant information for all reported sections are interpreted directly from user-supplied data. The user recognizes they are using this report at their own risk. For a full list of disclaimers and limitations see Section IV.

Section I: Genotype Summary

Genotypes called: 6 / 18

Drugs Gene Genotypes
Genotype Allele Functionality Phenotype
efavirenz
sertraline
CYP2B6 † ‡
*1/*5 Two Normal function alleles Normal Metabolizer
*1/*7 One Decreased function allele and one Normal function allele Intermediate Metabolizer

Genotypes based on missing variant input *.

amitriptyline
brivaracetam
citalopram
clobazam
clomipramine
clopidogrel
dexlansoprazole
doxepin
escitalopram
imipramine
lansoprazole
mavacamten
omeprazole
pantoprazole
sertraline
trimipramine
voriconazole
CYP2C19 † ‡
*2/*38 One No function allele and one Normal function allele Intermediate Metabolizer

Genotype based on missing variant input *.

avatrombopag
celecoxib
dronabinol
flurbiprofen
fluvastatin
fosphenytoin
ibuprofen
lornoxicam
meloxicam
phenytoin
piroxicam
siponimod
tenoxicam
warfarin
CYP2C9 † ‡
*1/*3 One 0.0 (No function) allele and one 1.0 (Normal function) allele Intermediate Metabolizer
*1/*18 One 1.0 (Normal function) allele and one Uncertain function allele Indeterminate
*1/*68 One 1.0 (Normal function) allele and one Uncertain function allele Indeterminate

Genotypes based on missing variant input *.

capecitabine
flucytosine
fluorouracil
tegafur
DPYD †
c.85T>C (*9A) 1.0 (Normal function) See drug section
c.496A>G 1.0 (Normal function) See drug section

Genotypes based on missing variant input *.

atorvastatin
fluvastatin
lovastatin
pitavastatin
pravastatin
rosuvastatin
simvastatin
SLCO1B1 † ‡
*1/*20 One Increased function allele and one Normal function allele Normal Function

Genotype based on missing variant input *.

azathioprine
mercaptopurine
thioguanine
TPMT † ‡
*1/*3A One No function allele and one Normal function allele Intermediate Metabolizer

Genotype based on missing variant input *.

* Some alleles were not considered for the genotype calls due to missing variant information. Please see Section III for details. Alleles that could not be considered due to missing input might change the metabolizer phenotype and possible recommendation.
† Check Section III for more details about this call.
‡ It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.
CPIC terms for allele function and phenotype are used for all CPIC genes. For non-CPIC genes, DPWG terms are used.
For a full list of disclaimers and limitations see Section IV.

Section II: Prescribing Recommendations

amitriptyline

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • CYP2C19:*2/*38;
    CYP2D6:Not called - no variant data provided
Phenotypes
CYP2C19:
Intermediate Metabolizer
CYP2D6:
No Result
Activity Scores
CYP2C19:
N/A
CYP2D6:
No Result
  • CYP2C19: Reduced metabolism of tertiary amines compared to normal metabolizers
  • CYP2D6: n/a
 Initiate therapy with recommended starting dose.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. 		Strong

Citations:

atorvastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

DPWG Guideline Annotation 1

Genotype
SLCO1B1:*1/*20
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
SLCO1B1:*1/*20
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

avatrombopag

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

azathioprine

The assigned genotype is *1/*3A; however, *3B/*3C cannot be ruled out without phased data.
Some position data used to define TPMT alleles is missing which may change the matched genotype. See TPMT in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
  • NUDT15: n/a
  • TPMT: Moderate to high concentrations of TGN metabolites; low concentrations of MeTIMP. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
 Based on TPMT status, start with reduced starting doses (30%-80% of normal dose) if normal starting dose is 2-3 mg/kg/day (e.g., 0.6 – 2.4 mg/kg/day), and adjust doses of azathioprine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11302950, 15606506, 16530532). NUDT15 genotype is not available. If thiopurines are required and NUDT15 status is unknown, monitor closely for toxicity.

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 Grade ≥ 2 leukopaenia occurs in 23% of these patients with normal therapy for immunosuppression. The genetic variation increases the quantity of the active metabolites of azathioprine and mercaptopurine. IMMUNOSUPPRESSION Start with 50% of the standard dose. Adjustment of the initial dose should be guided by toxicity (monitoring of blood counts) and effectiveness. Dose adjustment is not required for doses lower than 1.5 mg/kg per day for azathioprine or 0.75 mg/kg per day for mercaptopurine. Note: more stringent dose reductions are necessary if the patient is also NUDT15 IM or NUDT15 PM. Unspecified

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 "Consider...reduced dosages in patients with heterozygous [TPMT or NUDT15] deficiency...Because of the risk of increased toxicity, dosage reduction is recommended in patients known to have heterozygous deficiency of TPMT or NUDT15." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: TPMT and/or NUDT15 intermediate or poor metabolizers

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 "Alters systemic active metabolite concentration and dosage requirements. Results in higher adverse reaction risk (myelosuppression). Consider alternative therapy in poor metabolizers. Dosage reduction is recommended in intermediate metabolizers for NUDT15 or TPMT. Intermediate metabolizers for both genes may require more substantial dosage reductions. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

brivaracetam

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

FDA Label Annotation 1

Genotype
CYP2C19:*2/*38
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations and higher adverse reaction risk. Consider dosage reductions in poor metabolizers." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

capecitabine

Some position data used to define DPYD alleles is missing which may change the matched genotype. See DPYD in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on capecitabine. The guideline does not provide a recommendation for capecitabine in patients with a DPYD activity score of 2. No recommendation

FDA Label Annotation 1

Genotype
DPYD:c.85T>C (*9A);
DPYD:c.496A>G
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
DPYD:c.85T>C (*9A);
DPYD:c.496A>G
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.
‡ The DPYD genotype used to look up phenotype is inferred from the two lowest function haplotypes.

Citations:

celecoxib

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.

Other Considerations

IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

FDA Label Annotation 1

Genotypes
CYP2C9:*1/*3;
CYP2C9:*1/*18;
CYP2C9:*1/*68
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 poor metabolizers or *3 carriers

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations. Reduce starting dose to half of the lowest recommended dose in poor metabolizers. Consider alternative therapy in poor metabolizers with juvenile rheumatoid arthritis." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

citalopram

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects. Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose. 		Moderate

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1

Genotype
CYP2C19:*2/*38
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C19:*2/*38
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

clobazam

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

FDA Label Annotation 1

Genotype
CYP2C19:*2/*38
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic active metabolite concentrations. Poor metabolism results in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

clomipramine

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • CYP2C19:*2/*38;
    CYP2D6:Not called - no variant data provided
Phenotypes
CYP2C19:
Intermediate Metabolizer
CYP2D6:
No Result
Activity Scores
CYP2C19:
N/A
CYP2D6:
No Result
  • CYP2C19: Reduced metabolism of tertiary amines compared to normal metabolizers
  • CYP2D6: n/a
 Initiate therapy with recommended starting dose.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. 		Optional

DPWG Guideline Annotation 1, 2

Genotypes
CYP2C19:*2/*38;
CYP2D6:Not called - no variant data provided
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

clopidogrel

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
CVI ACS PCI

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events Avoid standard dose (75 mg) clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication.

Other Considerations

For cardiovascular indications of acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). ACS and/or PCI includes patients undergoing PCI for an ACS or non-ACS (elective) indication. 		Strong

CPIC Guideline Annotation

Population:
CVI non-ACS non-PCI

No Action
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events No recommendation

Other Considerations

For non-acute coronary syndrome (non-ACS) and non-percutaneous coronary intervention (non-PCI) cardiovascular indications. Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI. 		No recommendation

CPIC Guideline Annotation

Population:
NVI

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events Consider an alternative P2Y12 inhibitor at standard dose if clinically indicated and no contraindication.

Other Considerations

For neurovascular indications. Neurovascular disease includes acute ischemic stroke or transient ischemic attack, secondary prevention of stroke, or prevention of thromboembolic events following neurointerventional procedures such as carotid artery stenting and stent-assisted coiling of intracranial aneurysms. Alternative P2Y12 inhibitors not impacted by CYP2C19 genetic variants include ticagrelor and ticlopidine. Prasugrel is contraindicated in patients with a history of stroke or TIA. Given limited outcomes data for genotype-guided anti-platelet therapy for neurovascular indications, selection of therapy should depend on individual patient treatment goals and risks for adverse events. 		Moderate

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1

Genotype
CYP2C19:*2/*38
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

 "Results in lower systemic active metabolite concentrations, lower antiplatelet response, and may result in higher cardiovascular risk. Consider use of another platelet P2Y12 inhibitor." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

dexlansoprazole

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy. Optional

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 intermediate or poor metabolizer

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

doxepin

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • CYP2C19:*2/*38;
    CYP2D6:Not called - no variant data provided
Phenotypes
CYP2C19:
Intermediate Metabolizer
CYP2D6:
No Result
Activity Scores
CYP2C19:
N/A
CYP2D6:
No Result
  • CYP2C19: Reduced metabolism of tertiary amines compared to normal metabolizers
  • CYP2D6: n/a
 Initiate therapy with recommended starting dose.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. 		Optional

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

dronabinol

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

FDA Label Annotation

Population:
Unspecified

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Monitoring for increased adverse reactions is recommended in patients known to carry genetic variants associated with diminished CYP2C9 function." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "May result in higher systemic concentrations and higher adverse reaction risk. Monitor for adverse reactions." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

efavirenz

The assigned genotype is *1/*7; however, *5/*6 cannot be ruled out without phased data.
Some position data used to define CYP2B6 alleles is missing which may change the matched genotype. See CYP2B6 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
child >40kg_adult

No Action
Genotype
Phenotype

Normal Metabolizer

 CYP2B6: Normal efavirenz metabolism Initiate efavirenz with standard dosing (600 mg/day)

Other Considerations

The ENCORE study showed that in treatment-naïve patients randomized to initiate efavirenz-based regimens (combined with tenofovir and emtricitabine), 400 mg/day was non-inferior to 600 mg/day regardless of CYP2B6 genotype (PMID 24522178). 		Strong

CPIC Guideline Annotation

Population:
child >40kg_adult

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2B6: Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; increased risk of CNS adverse events Consider initiating efavirenz with decreased dose of 400 mg/day

Other Considerations

If therapeutic drug monitoring is available and a decreased efavirenz dose is prescribed, consider obtaining steady-state plasma efavirenz concentrations to ensure concentrations are in the suggested therapeutic range (~1 to 4 μg/mL). To prescribe efavirenz at a decreased dose of 400 mg/day or 200 mg/day in a multidrug regimen may require prescribing more than one pill once daily. If so, the provider should weigh the potential benefit of reduced dose against the potential detrimental impact of increased pill number. 		Moderate

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

Normal Metabolizer

 The guideline does not provide a description of the impact of a normal metabolizer phenotype on efavirenz. The guideline does not provide a recommendation for efavirenz in normal metabolizers. No recommendation

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 Genetic variations increase the efavirenz plasma concentration and therefore the risk of side effects. However, the efavirenz plasma concentration remains within the therapeutic range for the majority of patients. Determine the efavirenz plasma concentration if side effects occur and reduce the dose if needed. In 14 IM adults, a dose reduction to 400 mg/day (2/3rd of the standard dose) was sufficient to achieve therapeutic plasma concentrations and to reduce or resolve side effects. The therapeutic range established for efavirenz is 1000-4000 ng/ml. Unspecified

FDA PGx Association 1

Genotypes
CYP2B6:*1/*5;
CYP2B6:*1/*7
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

escitalopram

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Reduced metabolism when compared to CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects. Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.

Other Considerations

Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when adjusting dose. 		Moderate

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 ultrarapid, intermediate, or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "May alter systemic concentrations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

flucytosine

Some position data used to define DPYD alleles is missing which may change the matched genotype. See DPYD in Section III for for more information.
Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on flucytosine. The guideline does not provide a recommendation for flucytosine in patients with a DPYD activity score of 2. No recommendation
‡ The DPYD genotype used to look up phenotype is inferred from the two lowest function haplotypes.

fluorouracil

Some position data used to define DPYD alleles is missing which may change the matched genotype. See DPYD in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Metabolizer

Activity Score

2.0

 DPYD: Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. Strong

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on fluorouracil. The guideline does not provide a recommendation for fluorouracil in patients with a DPYD activity score of 2. No recommendation

FDA Label Annotation 1

Genotype
DPYD:c.85T>C (*9A);
DPYD:c.496A>G
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
DPYD:c.85T>C (*9A);
DPYD:c.496A>G
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.
‡ The DPYD genotype used to look up phenotype is inferred from the two lowest function haplotypes.

Citations:

flurbiprofen

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.

Other Considerations

IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

FDA Label Annotation 1

Genotypes
CYP2C9:*1/*3;
CYP2C9:*1/*18;
CYP2C9:*1/*68
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 poor metabolizers or *3 carriers

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations. Use a reduced dosage in poor metabolizers." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

fluvastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Dosing Info
Genotype
Phenotypes
CYP2C9:
Intermediate Metabolizer
SLCO1B1:
Normal Function
Activity Scores
CYP2C9:
1.0
SLCO1B1:
N/A
  • CYP2C9: Increased fluvastatin exposure as compared to normal metabolizer which may translate to increased myopathy risk.
  • SLCO1B1: Typical myopathy risk and statin exposure.
 Prescribe ≤40mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40mg needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus non-statin guideline directed medical therapy) (PMID: 30423391).

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function should be evaluated prior to initiating a statin. The effects of drug-drug interactions may be more pronounced resulting in a higher risk of myopathy. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotypes
CYP2C9:
Indeterminate
SLCO1B1:
Normal Function
Activity Scores
CYP2C9:
N/A
SLCO1B1:
N/A
  • CYP2C9: n/a
  • SLCO1B1: Typical myopathy risk and statin exposure.
 Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. CYP2C9 phenotype could not be assigned based on genotyping.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

Citations:

fosphenytoin

The displayed recommendation for CYP2C9 and phenytoin is ONLY valid for non-carriers of the HLA-B*15:02 high-risk allele. CPIC guidance: Fos-/Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of fos-/phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In HLA-B*15:02 carriers, carbamazepine should not be used as an alternative. Alternative medications such as oxcarbazepine, eslicarbazepine acetate, and lamotrigine have some evidence linking SJS/TEN with the HLA-B*15:02 allele, and thus caution should be used in choosing alternatives to phenytoin.
Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
PHT naive

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
  • CYP2C9: Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities.
  • HLA-B: n/a
 For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard. Moderate

CPIC Guideline Annotation

Population:
PHT use >3mos

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
  • CYP2C9: Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities.
  • HLA-B: n/a
 For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard. Moderate

CPIC Guideline Annotation

Population:
PHT naive

No Action
Genotypes
Phenotype

Indeterminate

Activity Scores
CYP2C9:
N/A
HLA-B:
N/A
  • CYP2C9: n/a
  • HLA-B: n/a
 No recommendation Unspecified

CPIC Guideline Annotation

Population:
PHT use >3mos

No Action
Genotypes
Phenotype

Indeterminate

Activity Scores
CYP2C9:
N/A
HLA-B:
N/A
  • CYP2C9: n/a
  • HLA-B: n/a
 No recommendation Unspecified

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
 "Consider avoiding CEREBYX [fosphenytoin] as an alternative to carbamazepine in patients who are positive for HLA-B*1502 or in CYP2C9*3 carriers. Should CEREBYX [fosphenytoin] be utilized for CYP2C9*3 carriers, consider starting at the lower end of the dosage range...[P]atients who are known to be intermediate or poor metabolizers may ultimately require lower doses to maintain similar steady-state concentrations compared to normal metabolizers. In patients who are known to be carriers of the decreased function CYP2C9*2 or *3 alleles (intermediate and poor metabolizers), consider starting at the low end of the dosage range and monitor serum concentrations to maintain total phenytoin concentrations of 10 to 20 mcg/mL." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

CYP2C9 intermediate or poor metabolizers

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "May result in higher systemic concentrations and higher adverse reaction risk (central nervous system toxicity). Consider starting at the lower end of the dosage range and monitor serum concentrations. Refer to FDA labeling for specific dosing recommendations. Carriers of CYP2C9*3 alleles may be at increased risk of severe cutaneous adverse reactions. Consider avoiding fosphenytoin as an alternative to carbamazepine in patients who are CYP2C9*3 carriers. Genotyping is not a substitute for clinical vigilance and patient management." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

ibuprofen

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.

Other Considerations

IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

FDA PGx Association 1

Genotypes
CYP2C9:*1/*3;
CYP2C9:*1/*18;
CYP2C9:*1/*68
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

imipramine

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • CYP2C19:*2/*38;
    CYP2D6:Not called - no variant data provided
Phenotypes
CYP2C19:
Intermediate Metabolizer
CYP2D6:
No Result
Activity Scores
CYP2C19:
N/A
CYP2D6:
No Result
  • CYP2C19: Reduced metabolism of tertiary amines compared to normal metabolizers
  • CYP2D6: n/a
 Initiate therapy with recommended starting dose.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. 		Optional

DPWG Guideline Annotation 1, 2

Genotypes
CYP2C19:*2/*38;
CYP2D6:Not called - no variant data provided
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

lansoprazole

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy. Optional

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
CYP2C19:*2/*38
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

lornoxicam

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events such as blood pressure and kidney function during course of therapy.

Other Considerations

IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Further caution should be taken with ibuprofen use in individuals carrying the CYP2C9*2 allele as it is in linkage disequilibrium with CYP2C8*3 and ibuprofen is also metabolized by CYP2C8. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

Citations:

lovastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

Citations:

mavacamten

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

FDA PGx Association [Pharmacogenetic Associations for which the Data Indicate a Potential Impact on Safety or Response]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations and may have higher adverse reaction risk (heart failure). Dosage is based on individual response. The dose titration and monitoring schedule accounts for differences due to CYP2C19 genetic variation, so adjustments based on CYP2C19 genotype are not necessary. Refer to FDA labeling for specific dosing recommendations and monitoring." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

meloxicam

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Initiate therapy with 50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 50% of the maximum recommended dose with caution. In accordance with the meloxicam prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady state is reached (at least 7 days). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider alternative therapy. Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).

Other Considerations

IMs might have a higher than normal risk of adverse events especially in individuals with other factors affecting clearance of these drugs such as hepatic impairment or advanced age. Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 poor metabolizers or *3 carriers

Dosing Info
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations. Consider dose reductions in poor metabolizers. Monitor patients for adverse reactions." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

mercaptopurine

The assigned genotype is *1/*3A; however, *3B/*3C cannot be ruled out without phased data.
Some position data used to define TPMT alleles is missing which may change the matched genotype. See TPMT in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
  • NUDT15: n/a
  • TPMT: Moderate to high concentrations of TGN metabolites; low concentrations of MeTIMP. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
 Based on TPMT status, start with reduced starting doses (30%-80% of normal dose) if normal starting dose is ≥ 75 mg/m2/day or ≥ 1.5 mg/kg/day (e.g., start at 22.5-60 mg/m2/day or 0.45-1.2 mg/kg/day) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing mercaptopurine over other agents (PMID 20354201,18685564, 8857546, 18987654, 20010622, 16401827, 11302950, 16530532, 9634537). If normal starting dose is already < 75 mg/m2/day or < 1.5 mg/kg/day, dose reduction may not be recommended. NUDT15 genotype result is not available. If thiopurines are required and either TPMT or NUDT15 status is unknown, monitor closely for toxicity.

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Strong

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 Grade ≥ 2 leukopaenia occurs in 23% of these patients with normal therapy for immunosuppression. The genetic variation increases the quantity of the active metabolites of azathioprine and mercaptopurine IMMUNOSUPPRESSION: Start with 50% of the standard dose. Adjustment of the initial dose should be guided by toxicity (monitoring of blood counts) and effectiveness. Dose adjustment is not required for doses lower than 1.5 mg/kg per day for azathioprine or 0.75 mg/kg per day for mercaptopurine. LEUKAEMIA: Start with 50% of the standard mercaptopurine dose, or start with the standard dose and reduce to 50% if side effects necessitate a dose reduction. It is not known whether dose reduction in advance results in the same efficacy as dose reduction based on toxicity. The initial dose should be adjusted based on toxicity (monitoring of the blood counts) and efficacy. Note: more stringent dose reductions are necessary if the patient is also NUDT15 IM or NUDT15 PM. Unspecified

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 The mercaptopurine (PURIXAN) label states: "Heterozygous Deficiency in TPMT and/or NUDT15 … Reduce the PURIXAN dosage based on tolerability. Most patients with heterozygous TPMT or NUDT15 deficiency tolerate recommended dosage, but some require dose reduction based on adverse reactions. Patients who are heterozygous for both TPMT and NUDT15 may require more substantial dose reductions.” See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: TPMT and/or NUDT15 intermediate or poor metabolizers

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 "Alters systemic active metabolite concentration and dosage requirements. Results in higher adverse reaction risk (myelosuppression). Initial dosages should be reduced in poor metabolizers; poor metabolizers generally tolerate 10% or less of the recommended dosage. Intermediate metabolizers may require dosage reductions based on tolerability. Intermediate metabolizers for both genes may require more substantial dosage reductions. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

omeprazole

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy. Optional

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Demonstrate a Potential Impact on Pharmacokinetic Properties Only]

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

pantoprazole

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Increased plasma concentration of PPI compared to CYP2C19 NMs; increased chance of efficacy and potentially toxicity Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy. Optional

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA Label Annotation 1

Genotype
CYP2C19:*2/*38
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Pediatrics; Affected subgroup: CYP2C19 intermediate or poor metabolizers

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations. Consider dosage reduction in children who are poor metabolizers. No dosage adjustment is needed for adult patients who are intermediate or poor metabolizers." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

phenytoin

The displayed recommendation for CYP2C9 and phenytoin is ONLY valid for non-carriers of the HLA-B*15:02 high-risk allele. CPIC guidance: Fos-/Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of fos-/phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In HLA-B*15:02 carriers, carbamazepine should not be used as an alternative. Alternative medications such as oxcarbazepine, eslicarbazepine acetate, and lamotrigine have some evidence linking SJS/TEN with the HLA-B*15:02 allele, and thus caution should be used in choosing alternatives to phenytoin.
Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
PHT naive

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
  • CYP2C9: Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities.
  • HLA-B: n/a
 For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard. Moderate

CPIC Guideline Annotation

Population:
PHT use >3mos

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
  • CYP2C9: Reduced phenytoin metabolism; Higher plasma concentrations will increase probability of toxicities.
  • HLA-B: n/a
 For first dose, use typical initial or loading dose. For subsequent doses, use approximately 25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to a usual standard. Moderate

CPIC Guideline Annotation

Population:
PHT naive

No Action
Genotypes
Phenotype

Indeterminate

Activity Scores
CYP2C9:
N/A
HLA-B:
N/A
  • CYP2C9: n/a
  • HLA-B: n/a
 No recommendation Unspecified

CPIC Guideline Annotation

Population:
PHT use >3mos

No Action
Genotypes
Phenotype

Indeterminate

Activity Scores
CYP2C9:
N/A
HLA-B:
N/A
  • CYP2C9: n/a
  • HLA-B: n/a
 No recommendation Unspecified

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 Genetic variation reduces conversion of phenytoin to inactive metabolites. This increases the risk of side effects. The life-threatening cutaneous side effects Stevens-Johnson Syndrome and toxic epidermal necrolysis may occur, especially in Asian patients.
  1. The loading dose does not need to be adjusted.
  2. For the other doses, use 75% of the standard dose and assess the dose based on effect and serum concentration after 7-10 days.
  3. Advise the patient to get in touch if side effects (such as ataxia, nystagmus, slurred speech, sedation or, especially in Asian patients, rash) occur.
 Unspecified

FDA Label Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Scores
CYP2C9:
1.0
HLA-B:
N/A
 "Patients who are intermediate or poor metabolizers of CYP2C9 substrates (e.g., *1/*3, *2/*2, *3/*3) may exhibit increased phenytoin serum concentrations compared to patients who are normal metabolizers (e.g., *1/*1). Thus, patients who are known to be intermediate or poor metabolizers may ultimately require lower doses of phenytoin to maintain similar steady-state concentrations compared to normal metabolizers...Consider avoiding DILANTIN [phenytoin] as an alternative to carbamazepine in patients who are positive for HLA-B*1502 or in CYP2C9*3 carriers." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

CYP2C9 intermediate or poor metabolizers

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "May result in higher systemic concentrations and higher adverse reaction risk (central nervous system toxicity). Refer to FDA labeling for specific dosing recommendations. Carriers of CYP2C9*3 alleles may be at increased risk of severe cutaneous adverse reactions. Consider avoiding phenytoin as an alternative to carbamazepine in patients who are CYP2C9*3 carriers. Genotyping is not a substitute for clinical vigilance and patient management." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

piroxicam

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).

Other Considerations

Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity. 		Moderate

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

FDA Label Annotation 1

Genotypes
CYP2C9:*1/*3;
CYP2C9:*1/*18;
CYP2C9:*1/*68
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations. Consider reducing dosage in poor metabolizers." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

pitavastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

Citations:

pravastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

Citations:

rosuvastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • ABCG2:Not called - no variant data provided;
    SLCO1B1:*1/*20
Phenotypes
ABCG2:
No Result
SLCO1B1:
Normal Function
  • ABCG2: n/a
  • SLCO1B1: Typical myopathy risk and statin exposure
 Based on SLCO1B1 status, prescribe desired starting dose and adjust doses based on disease-specific guidelines. ABCG2 genotype result is not available.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

DPWG Guideline Annotation 1

Genotype
SLCO1B1:*1/*20
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
SLCO1B1:*1/*20
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

sertraline

Some position data used to define CYP2B6 alleles is missing which may change the matched genotype. See CYP2B6 in Section III for for more information.
Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2B6:
Normal Metabolizer
CYP2C19:
Intermediate Metabolizer
  • CYP2B6: Normal metabolism of sertraline to less active compounds.
  • CYP2C19: Reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers.
 Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose. Moderate

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
Phenotypes
CYP2B6:
Intermediate Metabolizer
CYP2C19:
Intermediate Metabolizer
  • CYP2B6: Reduced metabolism of sertraline to less active compounds when compared to CYP2B6 normal metabolizers.
  • CYP2C19: Reduced metabolism of sertraline to less active compounds when compared to CYP2C19 normal metabolizers.
 Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers. Optional

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

simvastatin

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
Some position data used to define SLCO1B1 alleles is missing which may change the matched genotype. See SLCO1B1 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
Phenotype

Normal Function

 SLCO1B1: Typical myopathy risk and statin exposure Prescribe desired starting dose and adjust doses based on disease-specific guidelines.

Other Considerations

The potential for drug-drug interactions and dose limits based on renal and hepatic function and ancestry should be evaluated prior to initiating a statin. 		Strong

DPWG Guideline Annotation 1

Genotype
SLCO1B1:*1/*20
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association 1

Genotype
SLCO1B1:*1/*20
 
FDA PGx Association provides no genotype-based recommendations for this genotype, after evaluating the evidence.

Citations:

siponimod

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 Theoretically, the risk of adverse effects in increased, as the genetic variation results in higher plasma concentrations of siponimod. Use 50% of the normal maintenance dose. Reconsider the choice and the potential benefit of siponimod if the patient is also using a moderate CYP3A4 inducer, such as modafinil. For this genetic variation, a moderate CYP3A4 inducer results in a reduction in the exposure of siponimod by 49%, according to a pharmacokinetic model. Unspecified

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 The MAYZENT (siponimod) label states: "Initiate MAYZENT with a 4-day titration, as shown in Table 2... Do not use the starter pack for patients who will be titrated to the 1-mg maintenance dosage." "In patients with a CYP2C9 *1/*3 or *2/*3 genotype, after treatment titration (see Treatment Initiation), the recommended maintenance dosage of MAYZENT is 1 mg taken orally once daily starting on Day 5." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: CYP2C9 intermediate or poor metabolizers

Alternate Drug
Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Results in higher systemic concentrations. Adjust dosage based on genotype. Do not use in patients with CYP2C9 *3/*3 genotype. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

tegafur

Some position data used to define DPYD alleles is missing which may change the matched genotype. See DPYD in Section III for for more information.
Source Genes Implications Recommendation Classification

DPWG Guideline Annotation

Population:
Unspecified

No Action
Genotype
Phenotype

2.0 (Normal Metabolizer)

 The guideline does not provide a description of the impact of a DPYD activity score of 2 on tegafur. The guideline does not provide a recommendation for tegafur in patients with a DPYD activity score of 2. No recommendation
‡ The DPYD genotype used to look up phenotype is inferred from the two lowest function haplotypes.

Citations:

tenoxicam

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Alternate Drug
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 CYP2C9: Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo or choose an NSAID metabolized by CYP2C9 but with a shorter half-life (see CPIC THERAPEUTIC RECOMMENDATIONS FOR CELECOXIB, FLURBIPROFEN, LORNOXICAM, AND IBUPROFEN BASED ON CYP2C9 PHENOTYPE).

Other Considerations

Alternative therapies not primarily metabolized by CYP2C9 include aspirin, ketorolac, naproxen and sulindac. Selection of therapy will depend on individual patient treatment goals and risks for toxicity. 		Optional

CPIC Guideline Annotation

Population:
general

No Action
Genotypes
Phenotype

Indeterminate

Activity Score

N/A

 CYP2C9: n/a No recommendation No recommendation

Citations:

thioguanine

The assigned genotype is *1/*3A; however, *3B/*3C cannot be ruled out without phased data.
Some position data used to define TPMT alleles is missing which may change the matched genotype. See TPMT in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
  • NUDT15: n/a
  • TPMT: Moderate to high concentrations of TGN metabolites; but note that TGN after thioguanine are 5-10X higher than TGN after mercaptopurine or azathioprine. Increased risk of thiopurine-related leukopenia, neutropenia, myelosuppression
 Based on TPMT status, start with reduced doses (50% to 80% of normal dose) if normal starting dose is ≥ 40-60 mg/m2/day (e.g., 20-48 mg/m2/day) and adjust doses of thioguanine based on degree of myelosuppression and disease-specific guidelines. Allow 2-4 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, and depending on other therapy, emphasis should be on reducing thioguanine over other agents (PMID 20354201, 11037857). NUDT15 genotype is not available. If thiopurines are required and NUDT15 status is unknown, monitor closely for toxicity.

Other Considerations

Normal starting doses vary by race/ethnicity and treatment regimens. If standard dose is below normal recommended dose, dose reduction might not be recommended for intermediate metabolizers. 		Moderate

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 Genetic variation reduces conversion of thioguanine to inactive metabolites. This increases the risk of serious adverse events such as myelosuppression. IMMUNOSUPPRESSION: Start with 75% of the standard dose. Adjustment of the initial dose should be guided by toxicity (monitoring of blood counts) and efficacy. The frequency of monitoring should be increased. LEUKAEMIA: Start with 75% of the standard thioguanine dose, or start with the standard dose and reduce to 75% if side effects necessitate a dose reduction. It is not known whether dose reduction in advance results in the same efficacy as dose reduction based on toxicity. The initial dose should be adjusted based on toxicity (monitoring of the blood counts) and efficacy. Monitoring should be performed at an increased frequency. Note: more stringent dose reductions are necessary if the patient is also NUDT15 IM. Unspecified

FDA Label Annotation

Population:
Unspecified

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 "Most patients with heterozygous TPMT or NUDT15 deficiency tolerate recommended thioguanine doses, but some require dose reduction based on toxicities...Reduce the dosage based on tolerability." See label for more information. * Unspecified

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

Affected subgroup: TPMT and/or NUDT15 intermediate or poor metabolizers

Dosing Info
Genotype
  • NUDT15:Not called - no variant data provided;
    TPMT:*1/*3A
Phenotypes
NUDT15:
No Result
TPMT:
Intermediate Metabolizer
 "Alters systemic active metabolite concentration and dosage requirements. Results in higher adverse reaction risk (myelosuppression). Initial dosages should be reduced in poor metabolizers; poor metabolizers generally tolerate 10% or less of the recommended dosage. Intermediate metabolizers may require dosage reductions based on tolerability. Intermediate metabolizers for both genes may require more substantial dosage reductions. Refer to FDA labeling for specific dosing recommendations." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

trimipramine

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
general

No Action
Genotype
  • CYP2C19:*2/*38;
    CYP2D6:Not called - no variant data provided
Phenotypes
CYP2C19:
Intermediate Metabolizer
CYP2D6:
No Result
Activity Scores
CYP2C19:
N/A
CYP2D6:
No Result
  • CYP2C19: Reduced metabolism of tertiary amines compared to normal metabolizers
  • CYP2D6: n/a
 Initiate therapy with recommended starting dose.

Other Considerations

Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose. 		Optional

Citations:

voriconazole

Some position data used to define CYP2C19 alleles is missing which may change the matched genotype. See CYP2C19 in Section III for for more information.
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
adults

No Action
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers Initiate therapy with recommended standard of care dosing

Other Considerations

Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. 		Moderate

CPIC Guideline Annotation

Population:
pediatrics

No Action
Genotype
Phenotype

Intermediate Metabolizer

 CYP2C19: Higher dose-adjusted trough concentrations of voriconazole compared with normal metabolizers Initiate therapy with recommended standard of care dosing

Other Considerations

Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors, such as drug interactions, hepatic function, renal function, species, site of infection, therapeutic drug monitoring, and comorbidities. 		Moderate

DPWG Guideline Annotation 1

Genotype
CYP2C19:*2/*38
 
DPWG Guideline Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Indicate a Potential Impact on Safety or Response]

Affected subgroup: CYP2C19 intermediate or poor metabolizers

Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

 "Results in higher systemic concentrations and may result in higher adverse reaction risk." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

warfarin

Some position data used to define CYP2C9 alleles is missing which may change the matched genotype. See CYP2C9 in Section III for for more information.
Please follow the flow chart in figure 2 of the CPIC warfarin guideline to determine the appropriate dosing recommendation.
The CPIC warfarin guideline only considers a single SNV in VKORC1 (rs9923231), which has varying frequency among different ancestral populations, and largely explains the differences in average dose requirements between people of European, African, and Asian descents. While other functional variants in VKORC1 have been associated with warfarin resistance (high dose requirements), there are currently no CPIC recommendations for how to use these other variants in warfarin dosing. An alternate name for rs9923231 is -1639G>A (note that VKORC1 is on the negative chromosomal strand, so displayed alleles are complemented).
Source Genes Implications Recommendation Classification

CPIC Guideline Annotation

Population:
N/A
Genotypes
  • CYP2C9:*1/*3;
    CYP4F2:Not called - no variant data provided;
    VKORC1:Not called - no variant data provided;
    rs12777823:Unknown
  • CYP2C9:*1/*18;
    CYP4F2:Not called - no variant data provided;
    VKORC1:Not called - no variant data provided;
    rs12777823:Unknown
  • CYP2C9:*1/*68;
    CYP4F2:Not called - no variant data provided;
    VKORC1:Not called - no variant data provided;
    rs12777823:Unknown
Figure 2 from the CPIC guideline for warfarin

DPWG Guideline Annotation

Population:
Unspecified

Dosing Info
Genotype
Phenotype

Intermediate Metabolizer

 This gene variation reduces the conversion of warfarin to inactive metabolites. This can increase the risk of bleeding.
  1. use 65% of the standard initial dose. The genotype-specific initial dose and maintenance dose can be calculated using an algorithm, as used in EU-PACT. From day 6 on the standard algorithm without genotype information can be used to calculate the dose.
 Unspecified

FDA Label Annotation 1

Genotypes
CYP2C9:*1/*3;
CYP2C9:*1/*18;
CYP2C9:*1/*68;
VKORC1:Not called - no variant data provided
 
FDA Label Annotation provides no genotype-based recommendations for this genotype, after evaluating the evidence.

FDA PGx Association [Pharmacogenetic Associations for which the Data Support Therapeutic Management Recommendations]

CYP2C9 intermediate or poor metabolizers

Dosing Info
Other Guidance
Genotype
Phenotype

Intermediate Metabolizer

Activity Score

1.0

 "Alters systemic concentrations and dosage requirements. Select initial dosage, taking into account clinical and genetic factors. Monitor and adjust dosages based on INR." * Unspecified
* Text in quotation is taken directly from the FDA Label or FDA PGx Association table. For a label PDF with highlighted PGx content use the link in the Source column or go to PharmGKB.

Citations:

Section III: Allele Matching Details

  1. CYP2B6 allele match data
  2. CYP2C19 allele match data
  3. CYP2C9 allele match data
  4. DPYD allele match data
  5. SLCO1B1 allele match data
  6. TPMT allele match data

No data provided for ABCG2, CACNA1S, CFTR, CYP2D6, CYP3A4, CYP3A5, CYP4F2, G6PD, NUDT15, RYR1, UGT1A1, VKORC1.

CYP2B6 allele match data

Alleles Matched:
  • *1/*5
  • *1/*7
Phasing Status:

Unphased

It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Alleles Not Considered:

The following alleles are not considered due to 46 missing positions of the total 47 positions: *2, *3, *4, *6, *8, *9, *10, *11, *12, *13, *14, *15, *17, *18, *19, *20, *21, *22, *23, *24, *25, *26, *27, *28, *31, *32, *35, *36, *37, *38, *39, *40, *41, *42, *43, *44, *45, *46, *47, *48, *49

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The assigned genotype is *1/*7; however, *5/*6 cannot be ruled out without phased data.
The CYP2B6 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions either because the position is reference or missing.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr19:41016810 rs3211371 C/T C
  • *5 - Normal function
  • *7 - Decreased function
  • *33 - Uncertain function
  • *34 - Decreased function
chr19:40991224 rs34223104
Missing
 T
  • *22 - Uncertain function
  • *34 - Decreased function
  • *35 - Uncertain function
  • *36 - Decreased function
chr19:40991367 rs34883432
Missing
 A
  • *10 - Uncertain function
chr19:40991369 rs8192709
Missing
 C
  • *2 - Normal function
  • *10 - Uncertain function
chr19:40991381 rs33973337
Missing
 A
  • *17 - Normal function
chr19:40991388 rs33980385
Missing
 A
  • *17 - Normal function
chr19:40991390 rs33926104
Missing
 C
  • *17 - Normal function
chr19:40991391 rs34284776
Missing
 G
  • *17 - Normal function
chr19:40991441 rs35303484
Missing
 A
  • *11 - Uncertain function
chr19:41004015 rs281864907
Missing
 T
  • *38 - No function
chr19:41004125 rs36060847
Missing
 G
  • *12 - No function
chr19:41004133 rs148009906
Missing
 G
  • *44 - Uncertain function
chr19:41004158 rs186335453
Missing
 G
  • *35 - Uncertain function
chr19:41004303 rs139801276
Missing
 T
  • *35 - Uncertain function
chr19:41004377 rs12721655
Missing
 A
  • *8 - No function
  • *13 - No function
chr19:41004380 rs535039125
Missing
 C
  • *39 - Decreased function
chr19:41004381 rs35773040
Missing
 G
  • *14 - Uncertain function
chr19:41004406 rs145884402
Missing
 G
  • *35 - Uncertain function
chr19:41006919 rs3826711
Missing
 C
  • *26 - Decreased function
chr19:41006923 rs36056539
Missing
 C
  • *20 - Decreased function
chr19:41006936 rs3745274
Missing
 G
  • *6 - Decreased function
  • *7 - Decreased function
  • *9 - Decreased function
  • *13 - No function
  • *19 - Decreased function
  • *20 - Decreased function
  • *26 - Decreased function
  • *34 - Decreased function
  • *36 - Decreased function
  • *37 - Decreased function
  • *38 - No function
  • *39 - Decreased function
  • *40 - Decreased function
  • *41 - Decreased function
  • *42 - Decreased function
  • *43 - Decreased function
chr19:41006967 rs58871670
Missing
 G
  • *45 - Uncertain function
chr19:41006968 rs373489637
Missing
 T
  • *37 - Decreased function
chr19:41007013 rs36079186
Missing
 T
  • *27 - Uncertain function
  • *35 - Uncertain function
chr19:41009313
Missing
 A
  • *46 - Uncertain function
chr19:41009350 rs45482602
Missing
 C
  • *3 - Uncertain function
chr19:41009358 rs2279343
Missing
 A
  • *4 - Increased function
  • *6 - Decreased function
  • *7 - Decreased function
  • *13 - No function
  • *18 - No function
  • *19 - Decreased function
  • *20 - Decreased function
  • *26 - Decreased function
  • *34 - Decreased function
  • *36 - Decreased function
  • *37 - Decreased function
  • *38 - No function
  • *39 - Decreased function
  • *40 - Decreased function
  • *41 - Decreased function
  • *42 - Decreased function
  • *43 - Decreased function
chr19:41010006 rs139029625
Missing
 G
  • *35 - Uncertain function
chr19:41010088 rs34698757
Missing
 C
  • *28 - No function
chr19:41010108 rs193922917
Missing
 C
  • *31 - Normal function
chr19:41012316 rs28399499
Missing
 T
  • *18 - No function
chr19:41012339 rs34826503
Missing
 C
  • *19 - Decreased function
chr19:41012393 rs754621576
Missing
 T
  • *47 - Uncertain function
chr19:41012394 rs780991919
Missing
 A
  • *47 - Uncertain function
chr19:41012465 rs34097093
Missing
 C
  • *28 - No function
chr19:41012466 rs200458614
Missing
 G
  • *40 - Decreased function
chr19:41012471 rs201500445
Missing
 T
  • *41 - Decreased function
chr19:41012478 rs200238771
Missing
 T
  • *48 - Uncertain function
chr19:41012693 rs35979566
Missing
 T
  • *15 - Uncertain function
chr19:41012740 rs193922918
Missing
 G
  • *32 - Normal function
chr19:41012803 rs35010098
Missing
 C
  • *21 - Uncertain function
chr19:41016652 rs764288403
Missing
 G
  • *49 - Uncertain function
chr19:41016679 rs374099483
Missing
 G
  • *42 - Decreased function
chr19:41016726 rs3211369
Missing
 A
  • *23 - Uncertain function
chr19:41016741 rs117872433
Missing
 G
  • *43 - Decreased function
chr19:41016778 rs564083989
Missing
 G
  • *24 - Uncertain function
chr19:41016805
Missing
 A
  • *25 - Uncertain function

CYP2C19 allele match data

Allele Matched: *2/*38
Phasing Status:

Unphased

It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Alleles Not Considered:

The following alleles are not considered due to 32 missing positions of the total 34 positions: *16, *30, *34

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The CYP2C19 *38 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions either because the position is reference or missing.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr10:94781859 rs4244285 G/A G
  • *2 - No function
chr10:94842866 rs3758581 A/G A
  • *1 - Normal function
  • *2 - No function
  • *3 - No function
  • *4 - No function
  • *5 - No function
  • *6 - No function
  • *7 - No function
  • *8 - No function
  • *9 - Decreased function
  • *10 - Decreased function
  • *11 - Normal function
  • *12 - Uncertain function
  • *13 - Normal function
  • *14 - Uncertain function
  • *15 - Normal function
  • *17 - Increased function
  • *18 - Normal function
  • *19 - Decreased function
  • *22 - No function
  • *23 - Uncertain function
  • *24 - No function
  • *25 - Decreased function
  • *26 - Decreased function
  • *28 - Normal function
  • *29 - Uncertain function
  • *31 - Uncertain function
  • *32 - Uncertain function
  • *33 - Uncertain function
  • *35 - No function
  • *39 - Uncertain function
chr10:94761900 rs12248560
Missing
 C
  • *4 - No function
  • *17 - Increased function
chr10:94762706 rs28399504
Missing
 A
  • *4 - No function
chr10:94762712 rs367543002
Missing
 C
  • *34 - Uncertain function
chr10:94762715 rs367543003
Missing
 T
  • *34 - Uncertain function
chr10:94762755 rs55752064
Missing
 T
  • *14 - Uncertain function
chr10:94762760 rs17882687
Missing
 A
  • *15 - Normal function
  • *28 - Normal function
  • *35 - No function
  • *39 - Uncertain function
chr10:94762788 rs1564656981
Missing
 A
  • *29 - Uncertain function
chr10:94762856 rs1564657013
Missing
 A
  • *19 - Decreased function
chr10:94775106 rs145328984
Missing
 C
  • *30 - Uncertain function
chr10:94775121 rs1564660997
Missing
 C
  • *31 - Uncertain function
chr10:94775160 rs118203756
Missing
 G
  • *23 - Uncertain function
chr10:94775185 rs1288601658
Missing
 A
  • *32 - Uncertain function
chr10:94775367 rs12769205
Missing
 A
  • *2 - No function
  • *35 - No function
chr10:94775416 rs41291556
Missing
 T
  • *8 - No function
chr10:94775423 rs17885179
Missing
 A
  • *39 - Uncertain function
chr10:94775453 rs72552267
Missing
 G
  • *6 - No function
chr10:94775489 rs17884712
Missing
 G
  • *9 - Decreased function
chr10:94775507 rs58973490
Missing
 G
  • *2 - No function
  • *11 - Normal function
chr10:94780574 rs140278421
Missing
 G
  • *22 - No function
chr10:94780579 rs370803989
Missing
 G
  • *33 - Uncertain function
chr10:94780653 rs4986893
Missing
 G
  • *3 - No function
chr10:94781858 rs6413438
Missing
 C
  • *10 - Decreased function
chr10:94781944 rs375781227
Missing
 G
  • *26 - Decreased function
chr10:94781999 rs72558186
Missing
 T
  • *7 - No function
chr10:94842861 rs138142612
Missing
 G
  • *18 - Normal function
chr10:94842879 rs118203757
Missing
 G
  • *24 - No function
chr10:94842995 rs113934938
Missing
 G
  • *28 - Normal function
chr10:94849995 rs17879685
Missing
 C
  • *13 - Normal function
chr10:94852738 rs56337013
Missing
 C
  • *5 - No function
chr10:94852765 rs192154563
Missing
 C
  • *16 - Decreased function
chr10:94852785 rs118203759
Missing
 C
  • *25 - Decreased function
chr10:94852914 rs55640102
Missing
 A
  • *12 - Uncertain function

CYP2C9 allele match data

Alleles Matched:
  • *1/*3
  • *1/*18
  • *1/*68
Phasing Status:

Unphased

It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Alleles Not Considered:

The following alleles are not considered due to 79 missing positions of the total 80 positions: *2, *4, *5, *6, *7, *8, *9, *10, *11, *12, *13, *14, *15, *16, *17, *19, *20, *21, *22, *23, *24, *25, *26, *27, *28, *29, *30, *31, *32, *33, *34, *35, *36, *37, *38, *39, *40, *41, *42, *43, *44, *45, *46, *47, *48, *49, *50, *51, *52, *53, *54, *55, *56, *57, *58, *59, *60, *61, *62, *63, *64, *65, *66, *67, *69, *70, *71, *72, *73, *74, *75, *76, *77, *78, *79, *80, *81, *82, *83, *84, *85

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The CYP2C9 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions either because the position is reference or missing.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr10:94981296 rs1057910 A/C A
  • *3 - Activity Value 0.0 (No function)
  • *18 - Uncertain function
  • *68 - Uncertain function
chr10:94938683 rs114071557
Missing
 A
  • *36 - Uncertain function
chr10:94938719
Missing
 T
  • *80 - Unassigned
chr10:94938737 rs67807361
Missing
 C
  • *7 - Uncertain function
chr10:94938771 rs142240658
Missing
 C
  • *21 - Uncertain function
chr10:94938788
Missing
 C
  • *83 - Unassigned
chr10:94938800 rs1364419386
Missing
 G
  • *76 - Unassigned
chr10:94938803 rs2031308986
Missing
 A
  • *22 - Uncertain function
chr10:94938828 rs564813580
Missing
 A
  • *37 - Activity Value 0.5 (Decreased function)
chr10:94941897 rs371055887
Missing
 G
  • *20 - Uncertain function
chr10:94941915
Missing
 G
  • *23 - Activity Value 0.5 (Decreased function)
chr10:94941958 rs72558187
Missing
 T
  • *13 - Activity Value 0.0 (No function)
chr10:94941975
Missing
 G
  • *77 - Unassigned
chr10:94941976
Missing
 G
  • *38 - Activity Value 0.5 (Decreased function)
chr10:94941982 rs762239445
Missing
 G
  • *39 - Activity Value 0.0 (No function)
chr10:94942018
Missing
 T
  • *40 - Uncertain function
chr10:94942205 rs1304490498
Missing
 CAATGGAAA
GA
  • *25 - Activity Value 0.0 (No function)
chr10:94942216 rs774607211
Missing
 A
  • *41 - Uncertain function
chr10:94942230 rs767576260
Missing
 C
  • *43 - Activity Value 0.0 (No function)
chr10:94942231 rs12414460
Missing
 G
  • *42 - Activity Value 0.0 (No function)
chr10:94942233 rs375805362
Missing
 C
  • *62 - Uncertain function
chr10:94942234 rs72558189
Missing
 G
  • *14 - Activity Value 0.5 (Decreased function)
  • *35 - Activity Value 0.0 (No function)
chr10:94942243 rs1375956433
Missing
 T
  • *78 - Unassigned
chr10:94942249 rs200965026
Missing
 C
  • *26 - Activity Value 0.5 (Decreased function)
  • *44 - Activity Value 0.5 (Decreased function)
chr10:94942254 rs199523631
Missing
 C
  • *45 - Activity Value 0.0 (No function)
chr10:94942255 rs200183364
Missing
 G
  • *33 - Activity Value 0.0 (No function)
chr10:94942290 rs1799853
Missing
 C
  • *2 - Activity Value 0.5 (Decreased function)
  • *35 - Activity Value 0.0 (No function)
  • *61 - Activity Value 0.5 (Decreased function)
chr10:94942291 rs141489852
Missing
 G
  • *63 - Uncertain function
chr10:94942305 rs754487195
Missing
 G
  • *46 - Activity Value 0.5 (Decreased function)
chr10:94942306 rs1289704600
Missing
 C
  • *72 - Unknown function
chr10:94942308 rs17847037
Missing
 C
  • *73 - Unknown function
chr10:94942309 rs7900194
Missing
 G
  • *8 - Activity Value 0.5 (Decreased function)
  • *27 - Uncertain function
chr10:94947782 rs72558190
Missing
 C
  • *15 - Activity Value 0.0 (No function)
chr10:94947785 rs774550549
Missing
 C
  • *47 - Uncertain function
chr10:94947869
Missing
 A
  • *69 - Uncertain function
chr10:94947907
Missing
 A
  • *57 - Unknown function
chr10:94947917 rs1326630788
Missing
 T
  • *48 - Uncertain function
chr10:94947938 rs2031531005
Missing
 A
  • *28 - Activity Value 0.5 (Decreased function)
chr10:94947939 rs370100007
Missing
 G
  • *74 - Unknown function
chr10:94949129
Missing
 A
  • *49 - Uncertain function
chr10:94949144
Missing
 C
  • *50 - Activity Value 0.5 (Decreased function)
chr10:94949145 rs772782449
Missing
 C
  • *82 - Unassigned
chr10:94949161
Missing
 AT
  • *85 - Unassigned
chr10:94949217 rs2256871
Missing
 A
  • *9 - Activity Value 1.0 (Normal function)
chr10:94949280 rs9332130
Missing
 A
  • *10 - Uncertain function
  • *71 - Uncertain function
chr10:94949281 rs9332131
Missing
 GA
  • *6 - Activity Value 0.0 (No function)
chr10:94972119 rs182132442
Missing
 C
  • *29 - Activity Value 0.5 (Decreased function)
chr10:94972123
Missing
 C
  • *64 - Uncertain function
chr10:94972134
Missing
 A
  • *51 - Uncertain function
chr10:94972179 rs72558192
Missing
 A
  • *16 - Activity Value 0.5 (Decreased function)
chr10:94972180 rs988617574
Missing
 C
  • *52 - Activity Value 0.0 (No function)
chr10:94972183
Missing
 A
  • *81 - Unassigned
chr10:94972233 rs1237225311
Missing
 C
  • *53 - Uncertain function
chr10:94981199
Missing
 G
  • *65 - Uncertain function
chr10:94981201 rs57505750
Missing
 T
  • *31 - Activity Value 0.5 (Decreased function)
chr10:94981224 rs28371685
Missing
 C
  • *11 - Activity Value 0.5 (Decreased function)
chr10:94981225 rs367826293
Missing
 G
  • *34 - Uncertain function
chr10:94981230 rs1274535931
Missing
 C
  • *58 - Uncertain function
chr10:94981250 rs750820937
Missing
 C
  • *54 - Uncertain function
chr10:94981258 rs1297714792
Missing
 C
  • *79 - Unassigned
chr10:94981281 rs749060448
Missing
 G
  • *24 - Activity Value 0.0 (No function)
chr10:94981297 rs56165452
Missing
 T
  • *4 - Activity Value 0.5 (Decreased function)
chr10:94981301 rs28371686
Missing
 C
  • *5 - Activity Value 0.5 (Decreased function)
chr10:94981302 rs1250577724
Missing
 C
  • *55 - Activity Value 0.5 (Decreased function)
chr10:94981305 rs578144976
Missing
 C
  • *66 - Uncertain function
chr10:94981365
Missing
 C
  • *17 - Uncertain function
chr10:94981371 rs542577750
Missing
 G
  • *68 - Uncertain function
chr10:94986042 rs764211126
Missing
 A
  • *56 - Uncertain function
chr10:94986073 rs72558193
Missing
 A
  • *18 - Uncertain function
chr10:94986136 rs1254213342
Missing
 A
  • *75 - Unknown function
chr10:94986174 rs1441296358
Missing
 G
  • *84 - Unassigned
chr10:94988852 rs776908257
Missing
 C
  • *67 - Uncertain function
chr10:94988855
Missing
 A
  • *59 - Uncertain function
chr10:94988880
Missing
 G
  • *70 - Uncertain function
chr10:94988917 rs769942899
Missing
 G
  • *19 - Uncertain function
chr10:94988925 rs202201137
Missing
 A
  • *61 - Activity Value 0.5 (Decreased function)
chr10:94988955 rs767284820
Missing
 T
  • *60 - Uncertain function
chr10:94988984 rs781583846
Missing
 G
  • *30 - Activity Value 0.5 (Decreased function)
chr10:94989020 rs9332239
Missing
 C
  • *12 - Activity Value 0.5 (Decreased function)
  • *71 - Uncertain function
chr10:94989023 rs868182778
Missing
 G
  • *32 - Uncertain function

Other Positions of Interest

Position in VCF RSID Call in VCF
chr10:94645745 rs12777823 missing

DPYD allele match data

Variants Matched:
  • c.85T>C (*9A)
  • c.496A>G
Phasing Status:

Unphased

Alleles Not Considered:

The following alleles are not considered due to 81 missing positions of the total 83 positions: c.46C>G, c.61C>T, c.62G>A, c.295_298delTCAT (*7), c.313G>A, c.343A>G, c.451A>G, c.498G>A, c.525G>A, c.557A>G, c.601A>C, c.632A>G, c.703C>T (*8), c.775A>G, c.868A>G, c.929T>C, c.934C>T, c.967G>A, c.1003G>T (*11), c.1024G>A, c.1057C>T, c.1108A>G, c.1129-5923C>G, c.1129-5923C>G, c.1236G>A (HapB3), c.1156G>T (*12), c.1180C>T, c.1181G>T, c.1218G>A, c.1260T>A, c.1278G>T, c.1294G>A, c.1314T>G, c.1349C>T, c.1358C>G, c.1371C>T, c.1403C>A, c.1475C>T, c.1484A>G, c.1519G>A, c.1543G>A, c.1577C>G, c.1601G>A (*4), c.1615G>A, c.1627A>G (*5), c.1679T>G (*13), c.1682G>T, c.1774C>T, c.1775G>A, c.1777G>A, c.1796T>C, c.1896T>C, c.1898delC (*3), c.1905+1G>A (*2A), c.1905C>G, c.1906A>C, c.1990G>T, c.2021G>A, c.2161G>A, c.2186C>T, c.2194G>A (*6), c.2195T>G, c.2279C>T, c.2303C>A, c.2336C>A, c.2482G>A, c.2582A>G, c.2623A>C, c.2639G>T, c.2656C>T, c.2657G>A (*9B), c.2846A>T, c.2872A>G, c.2915A>G, c.2921A>T, c.2933A>G, c.2977C>T, c.2978T>G, c.2983G>T (*10), c.3049G>A, c.3061G>C, c.3067C>A

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The two lowest activity values (variant activity scores, see CPIC guideline PMID:29152729) are used for unphased data and the lowest activity value per allele is used for phased data to determine the gene activity score and phenotype to retrieve prescribing recommendations.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr1:97699535 rs2297595 T/C T
  • c.496A>G - Activity Value 1.0 (Normal function)
chr1:97883329 rs1801265 A/G A
  • c.85T>C (*9A) - Activity Value 1.0 (Normal function)
chr1:97078987 rs114096998
Missing
 G
  • c.3067C>A - Activity Value 1.0 (Normal function)
chr1:97078993 rs148799944
Missing
 C
  • c.3061G>C - Activity Value 1.0 (Normal function)
chr1:97079005 rs140114515
Missing
 C
  • c.3049G>A - Activity Value 1.0 (Normal function)
chr1:97079071 rs1801268
Missing
 C
  • c.2983G>T (*10) - Activity Value 0.0 (No function)
chr1:97079076 rs139459586
Missing
 A
  • c.2978T>G - Activity Value 1.0 (Normal function)
chr1:97079077 rs202144771
Missing
 G
  • c.2977C>T - Activity Value 1.0 (Normal function)
chr1:97079121 rs72547601
Missing
 T
  • c.2933A>G - Activity Value 0.0 (No function)
chr1:97079133 rs72547602
Missing
 T
  • c.2921A>T - Activity Value 1.0 (Normal function)
chr1:97079139 rs145529148
Missing
 T
  • c.2915A>G - Activity Value 1.0 (Normal function)
chr1:97082365 rs141044036
Missing
 T
  • c.2872A>G - Activity Value 0.0 (No function)
chr1:97082391 rs67376798
Missing
 T
  • c.2846A>T - Activity Value 0.5 (Decreased function)
chr1:97098598 rs1801267
Missing
 C
  • c.2657G>A (*9B) - Activity Value 1.0 (Normal function)
chr1:97098599 rs147545709
Missing
 G
  • c.2656C>T - Activity Value 1.0 (Normal function)
chr1:97098616 rs55674432
Missing
 C
  • c.2639G>T - Activity Value 0.0 (No function)
chr1:97098632 rs201035051
Missing
 T
  • c.2623A>C - Activity Value 1.0 (Normal function)
chr1:97193109 rs60139309
Missing
 T
  • c.2582A>G - Activity Value 1.0 (Normal function)
chr1:97193209 rs200687447
Missing
 C
  • c.2482G>A - Activity Value 1.0 (Normal function)
chr1:97234958 rs199634007
Missing
 G
  • c.2336C>A - Activity Value 1.0 (Normal function)
chr1:97234991 rs56005131
Missing
 G
  • c.2303C>A - Activity Value 1.0 (Normal function)
chr1:97305279 rs112766203
Missing
 G
  • c.2279C>T - Activity Value 0.5 (Decreased function)
chr1:97305363 rs60511679
Missing
 A
  • c.2195T>G - Activity Value 1.0 (Normal function)
chr1:97305364 rs1801160
Missing
 C
  • c.2194G>A (*6) - Activity Value 1.0 (Normal function)
chr1:97305372 rs146529561
Missing
 G
  • c.2186C>T - Activity Value 1.0 (Normal function)
chr1:97306195 rs145548112
Missing
 C
  • c.2161G>A - Activity Value 1.0 (Normal function)
chr1:97373598 rs137999090
Missing
 C
  • c.2021G>A - Activity Value 0.0 (No function)
chr1:97373629 rs138545885
Missing
 C
  • c.1990G>T - Activity Value 1.0 (Normal function)
chr1:97382461 rs55971861
Missing
 T
  • c.1906A>C - Activity Value 1.0 (Normal function)
chr1:97450058 rs3918290
Missing
 C
  • c.1905+1G>A (*2A) - Activity Value 0.0 (No function)
chr1:97450059 rs3918289
Missing
 G
  • c.1905C>G - Activity Value 1.0 (Normal function)
chr1:97450065 rs72549303
Missing
 TG
  • c.1898delC (*3) - Activity Value 0.0 (No function)
chr1:97450068 rs17376848
Missing
 A
  • c.1896T>C - Activity Value 1.0 (Normal function)
chr1:97450168 rs147601618
Missing
 A
  • c.1796T>C - Activity Value 1.0 (Normal function)
chr1:97450187 rs145773863
Missing
 C
  • c.1777G>A - Activity Value 0.0 (No function)
chr1:97450189 rs138616379
Missing
 C
  • c.1775G>A - Activity Value 0.0 (No function)
chr1:97450190 rs59086055
Missing
 G
  • c.1774C>T - Activity Value 0.0 (No function)
chr1:97515784 rs201615754
Missing
 C
  • c.1682G>T - Activity Value 1.0 (Normal function)
chr1:97515787 rs55886062
Missing
 A
  • c.1679T>G (*13) - Activity Value 0.0 (No function)
chr1:97515839 rs1801159
Missing
 T
  • c.1627A>G (*5) - Activity Value 1.0 (Normal function)
chr1:97515851 rs142619737
Missing
 C
  • c.1615G>A - Activity Value 1.0 (Normal function)
chr1:97515865 rs1801158
Missing
 C
  • c.1601G>A (*4) - Activity Value 1.0 (Normal function)
chr1:97515889 rs190951787
Missing
 G
  • c.1577C>G - Activity Value 1.0 (Normal function)
chr1:97515923 rs148994843
Missing
 C
  • c.1543G>A - Activity Value 1.0 (Normal function)
chr1:97549565 rs138391898
Missing
 C
  • c.1519G>A - Activity Value 1.0 (Normal function)
chr1:97549600 rs111858276
Missing
 T
  • c.1484A>G - Activity Value 0.0 (No function)
chr1:97549609 rs72549304
Missing
 G
  • c.1475C>T - Activity Value 0.0 (No function)
chr1:97549681 rs199549923
Missing
 G
  • c.1403C>A - Activity Value 1.0 (Normal function)
chr1:97549713 rs57918000
Missing
 G
  • c.1371C>T - Activity Value 1.0 (Normal function)
chr1:97549726 rs144395748
Missing
 G
  • c.1358C>G - Activity Value 1.0 (Normal function)
chr1:97549735 rs72975710
Missing
 G
  • c.1349C>T - Activity Value 1.0 (Normal function)
chr1:97573785 rs186169810
Missing
 A
  • c.1314T>G - Activity Value 0.5 (Decreased function)
chr1:97573805 rs142512579
Missing
 C
  • c.1294G>A - Activity Value 1.0 (Normal function)
chr1:97573821 rs764666241
Missing
 C
  • c.1278G>T - Activity Value 1.0 (Normal function)
chr1:97573839 rs200064537
Missing
 A
  • c.1260T>A - Activity Value 1.0 (Normal function)
chr1:97573863 rs56038477
Missing
 C
  • c.1129-5923C>G, c.1236G>A (HapB3) - Activity Value 0.5 (Decreased function)
chr1:97573881 rs61622928
Missing
 C
  • c.1218G>A - Activity Value 1.0 (Normal function)
chr1:97573918 rs143815742
Missing
 C
  • c.1181G>T - Activity Value 1.0 (Normal function)
chr1:97573919 rs140602333
Missing
 G
  • c.1180C>T - Activity Value 1.0 (Normal function)
chr1:97573943 rs78060119
Missing
 C
  • c.1156G>T (*12) - Activity Value 0.0 (No function)
chr1:97579893 rs75017182
Missing
 G
  • c.1129-5923C>G - Activity Value 0.5 (Decreased function)
  • c.1129-5923C>G, c.1236G>A (HapB3) - Activity Value 0.5 (Decreased function)
chr1:97593238 rs72549305
Missing
 T
  • c.1108A>G - Activity Value 1.0 (Normal function)
chr1:97593289 rs143154602
Missing
 G
  • c.1057C>T - Activity Value 0.0 (No function)
chr1:97593322 rs183385770
Missing
 C
  • c.1024G>A - Activity Value 0.0 (No function)
chr1:97593343 rs72549306
Missing
 C
  • c.1003G>T (*11) - Activity Value 1.0 (Normal function)
chr1:97593379 rs201018345
Missing
 C
  • c.967G>A - Activity Value 1.0 (Normal function)
chr1:97595083 rs145112791
Missing
 G
  • c.934C>T - Activity Value 1.0 (Normal function)
chr1:97595088 rs150437414
Missing
 A
  • c.929T>C - Activity Value 1.0 (Normal function)
chr1:97595149 rs146356975
Missing
 T
  • c.868A>G - Activity Value 0.5 (Decreased function)
chr1:97679170 rs45589337
Missing
 T
  • c.775A>G - Activity Value 1.0 (Normal function)
chr1:97691776 rs1801266
Missing
 G
  • c.703C>T (*8) - Activity Value 0.0 (No function)
chr1:97699399 rs72549307
Missing
 T
  • c.632A>G - Activity Value 0.0 (No function)
chr1:97699430 rs72549308
Missing
 T
  • c.601A>C - Activity Value 0.0 (No function)
chr1:97699474 rs115232898
Missing
 T
  • c.557A>G - Activity Value 0.5 (Decreased function)
chr1:97699506 rs6670886
Missing
 C
  • c.525G>A - Activity Value 1.0 (Normal function)
chr1:97699533 rs139834141
Missing
 C
  • c.498G>A - Activity Value 1.0 (Normal function)
chr1:97721542 rs200562975
Missing
 T
  • c.451A>G - Activity Value 1.0 (Normal function)
chr1:97721650 rs141462178
Missing
 T
  • c.343A>G - Activity Value 1.0 (Normal function)
chr1:97740400 rs150385342
Missing
 C
  • c.313G>A - Activity Value 1.0 (Normal function)
chr1:97740410 rs72549309
Missing
 GATGA
  • c.295_298delTCAT (*7) - Activity Value 0.0 (No function)
chr1:97883352 rs80081766
Missing
 C
  • c.62G>A - Activity Value 1.0 (Normal function)
chr1:97883353 rs72549310
Missing
 G
  • c.61C>T - Activity Value 0.0 (No function)
chr1:97883368 rs150036960
Missing
 G
  • c.46C>G - Activity Value 1.0 (Normal function)

SLCO1B1 allele match data

Allele Matched: *1/*20
Phasing Status:

Unphased

It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Alleles Not Considered:

The following alleles are not considered due to 29 missing positions of the total 31 positions: *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *12, *13, *16, *23, *26, *34, *36, *38, *41, *45

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The assigned genotype is*1/*20; however, *19/*37 cannot be ruled out without phased data.
The SLCO1B1 genotype (star nomenclature) will be displayed if determinable with the provided VCF based on the SLCO1B1 star allele definition published by CPIC and recommendations are provided based on the genotype.

In case no genotype can be determined, recommendations are based on the rs4149056 genotype alone as per guideline. The minor C allele at rs4149056 defines SLCO1B1*5.
The SLCO1B1 *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions either because the position is reference or missing.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr12:21176804 rs2306283 A/G A
  • *14 - Increased function
  • *15 - No function
  • *20 - Increased function
  • *24 - Uncertain function
  • *25 - Uncertain function
  • *27 - Uncertain function
  • *28 - Uncertain function
  • *29 - Uncertain function
  • *30 - Uncertain function
  • *31 - No function
  • *32 - Uncertain function
  • *33 - Uncertain function
  • *37 - Normal function
  • *39 - Uncertain function
  • *42 - Uncertain function
  • *43 - Unknown function
  • *44 - Unknown function
  • *46 - No function
  • *47 - No function
chr12:21239042 rs34671512 A/C A
  • *19 - Uncertain function
  • *20 - Increased function
  • *40 - Uncertain function
chr12:21172734 rs139257324
Missing
 C
  • *33 - Uncertain function
chr12:21172776 rs373327528
Missing
 G
  • *23 - No function
chr12:21172782 rs56101265
Missing
 T
  • *2 - Uncertain function
  • *12 - Uncertain function
chr12:21174595 rs56061388
Missing
 T
  • *3 - Uncertain function
  • *13 - Uncertain function
chr12:21176868 rs2306282
Missing
 A
  • *16 - Uncertain function
chr12:21176871
Missing
 G
  • *38 - Uncertain function
chr12:21176879 rs11045819
Missing
 C
  • *4 - Uncertain function
  • *14 - Increased function
  • *25 - Uncertain function
  • *32 - Uncertain function
  • *43 - Unknown function
chr12:21176883 rs72559745
Missing
 A
  • *3 - Uncertain function
  • *13 - Uncertain function
chr12:21176898 rs77271279
Missing
 G
  • *41 - Uncertain function
chr12:21178612 rs141467543
Missing
 A
  • *42 - Uncertain function
chr12:21178615 rs4149056
Missing
 T
  • *5 - No function
  • *15 - No function
  • *40 - Uncertain function
  • *46 - No function
  • *47 - No function
chr12:21178957 rs79135870
Missing
 A
  • *30 - Uncertain function
chr12:21196951 rs11045852
Missing
 A
  • *24 - Uncertain function
  • *25 - Uncertain function
  • *28 - Uncertain function
  • *32 - Uncertain function
  • *33 - Uncertain function
  • *43 - Unknown function
  • *44 - Unknown function
chr12:21196975 rs183501729
Missing
 C
  • *39 - Uncertain function
chr12:21196976 rs11045853
Missing
 G
  • *25 - Uncertain function
  • *28 - Uncertain function
  • *33 - Uncertain function
chr12:21200544 rs72559747
Missing
 C
  • *47 - No function
chr12:21200595 rs55901008
Missing
 T
  • *6 - Uncertain function
chr12:21202553 rs1228465562
Missing
 T
  • *36 - Uncertain function
chr12:21202555 rs59113707
Missing
 C
  • *27 - Uncertain function
chr12:21202649 rs56387224
Missing
 A
  • *7 - Uncertain function
chr12:21202664 rs142965323
Missing
 G
  • *26 - Uncertain function
chr12:21205921 rs72559748
Missing
 A
  • *8 - Uncertain function
chr12:21205999 rs59502379
Missing
 G
  • *9 - No function
  • *31 - No function
chr12:21206031 rs74064213
Missing
 A
  • *43 - Unknown function
  • *44 - Unknown function
chr12:21222355 rs71581941
Missing
 C
  • *45 - Unknown function
  • *46 - No function
chr12:21239077 rs56199088
Missing
 A
  • *10 - Uncertain function
  • *12 - Uncertain function
chr12:21239113 rs55737008
Missing
 A
  • *11 - Uncertain function
  • *13 - Uncertain function
chr12:21239145 rs200995543
Missing
 C
  • *34 - Uncertain function
chr12:21239158 rs140790673
Missing
 C
  • *29 - Uncertain function

TPMT allele match data

Allele Matched: *1/*3A
Phasing Status:

Unphased

It reports the genotype(s) that receive the highest score during the matcher process. In case of unphased data, additional genotypes might be possible and cannot be ruled out.

Alleles Not Considered:

The following alleles are not considered due to 41 missing positions of the total 43 positions: *2, *4, *5, *6, *7, *8, *9, *10, *11, *12, *13, *14, *15, *16, *17, *18, *19, *20, *21, *22, *23, *24, *25, *26, *27, *28, *29, *30, *31, *32, *33, *34, *35, *36, *37, *38, *39, *40, *42, *43, *44

Carriage of these alleles might result in a different phenotype and different guideline recommendations.

The assigned genotype is *1/*3A; however, *3B/*3C cannot be ruled out without phased data.
The TPMT *1 allele assignment is characterized by the absence of variants at the positions that are included in the underlying allele definitions either because the position is reference or missing.

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles and Function Warnings
chr6:18130687 rs1142345 T/C T
  • *3A - No function
  • *3C - No function
  • *41 - No function
chr6:18138997 rs1800460 C/T C
  • *3A - No function
  • *3B - No function
chr6:18130694 rs150900439
Missing
 T
  • *20 - Uncertain function
chr6:18130725 rs72552736
Missing
 A
  • *7 - Uncertain function
chr6:18130729 rs139392616
Missing
 C
  • *40 - Uncertain function
chr6:18130758 rs398122996
Missing
 A
  • *37 - Uncertain function
chr6:18130762 rs56161402
Missing
 C
  • *8 - Uncertain function
chr6:18130772 rs377085266
Missing
 A
  • *25 - Uncertain function
chr6:18130781 rs1800584
Missing
 C
  • *4 - No function
chr6:18132136 rs72556347
Missing
 A
  • *26 - Uncertain function
chr6:18132147 rs79901429
Missing
 A
  • *31 - Uncertain function
chr6:18132163
Missing
 C
  • *36 - Unknown function
chr6:18133845 rs75543815
Missing
 T
  • *6 - Uncertain function
chr6:18133847 rs6921269
Missing
 C
  • *24 - Uncertain function
chr6:18133870 rs772832951
Missing
 A
  • *38 - Unknown function
chr6:18133884 rs74423290
Missing
 G
  • *23 - No function
chr6:18133887 rs201695576
Missing
 T
  • *44 - Unassigned
chr6:18133890 rs9333570
Missing
 C
  • *15 - No function
chr6:18138969 rs144041067
Missing
 C
  • *16 - Uncertain function
  • *22 - Uncertain function
chr6:18138970 rs112339338
Missing
 G
  • *33 - Uncertain function
chr6:18139027 rs72552737
Missing
 C
  • *10 - Uncertain function
chr6:18139689 rs72552738
Missing
 C
  • *11 - No function
chr6:18139710 rs200220210
Missing
 G
  • *12 - Uncertain function
chr6:18143597
Missing
 T
  • *19 - Uncertain function
chr6:18143606 rs151149760
Missing
 T
  • *9 - Uncertain function
chr6:18143613
Missing
 C
  • *28 - Uncertain function
chr6:18143622 rs115106679
Missing
 C
  • *32 - Uncertain function
chr6:18143643
Missing
 A
  • *27 - Uncertain function
chr6:18143700 rs753545734
Missing
 C
  • *43 - Unassigned
chr6:18143718 rs111901354
Missing
 G
  • *34 - Uncertain function
chr6:18143724 rs1800462
Missing
 C
  • *2 - No function
chr6:18143728 rs1256618794
Missing
 C
  • *43 - Unassigned
chr6:18147838 rs281874771
Missing
 G
  • *39 - Uncertain function
chr6:18147845 rs777686348
Missing
 C
  • *18 - Uncertain function
chr6:18147851 rs200591577
Missing
 G
  • *21 - Uncertain function
chr6:18147856
Missing
 A
  • *35 - Unknown function
chr6:18147910 rs72552740
Missing
 A
  • *5 - Uncertain function
chr6:18149004
Missing
 G
  • *17 - Uncertain function
chr6:18149022 rs750424422
Missing
 C
  • *30 - Unknown function
chr6:18149032 rs759836180
Missing
 C
  • *42 - Unassigned
chr6:18149045 rs72552742
Missing
 T
  • *13 - Uncertain function
chr6:18149126 rs267607275
Missing
 A
  • *29 - No function
chr6:18149127 rs9333569
Missing
 T
  • *14 - No function

Disclaimers and Other Information

Liability: This report assumes no responsibility for any injury to person or damage to persons or property arising out of, or related to any use of this report, or for any errors or omissions. The user recognizes that this report is a research tool and that they are using this report at their own risk.

A. Allele and Genotype Determination

  1. This report uses gene allele definitions included in the CPIC database, with exceptions "CYP3A4, DPYD, G6PD, NAT2, SLCO1B1, RYR1". For allele definitions and the positions used in this report, see the gene definition tables.

  2. Genes with DPWG recommendations that are not included in CPIC are discussed in Section C.

  3. This report results are dependent on the supplied VCF calls for the queried positions. For technical information about input formatting and requirements, please refer to the relevant documentation. This report does not assume any reference calls for positions missing from the submitted VCF file; all missing queried positions are not considered in the allele determination process. Missing positions might alter the assigned genotype and subsequent phenotype prediction and CPIC recommendation. If the supplied VCF file has missing positions, those positions will be noted in Section III: Allele Matching Details for each gene of this report. For the most reliable allele determination, reference calls as well as variant calls in the VCF file for every queried position must be provided by the user. If an allele that includes a missing position is defined by an additional position(s) for which calls are provided, the allele will be considered in the matching process based on the available information. This might lead to the output of multiple possible genotypes that received the same highest matching score. In addition, alternate calls with a lower score is also possible. For instructions on getting this report to output all possible matching genotypes, consult the relevant documentation.

  4. For cytochrome P450 genes, TPMT, NUDT15, UGT1A1, and SLCO1B1, the *1 allele is defined by the absence of variation specified in the gene definition tables. This allele cannot be identified by variants; rather, *1 is assigned by default when no variation for the queried positions is reported in the submitted VCF file. The same is true for all other genes with multiple variant positions in the definition table (CACNA1S, CFTR, DPYD, RYR1): the reference sequence is the default result when variants are not reported in the VCF file. It is always possible un-interrogated variation can occur which could potentially affect allele function, but because it is undetected, the assignment would be defaulted to a *1 (or reference) allele and normal function.

  5. For all genes, variation reported in the VCF file but NOT included in the gene definition table will not be considered during allele assignment. There is a possibility that any such variation results in a reduced or no activity allele which could lead to inaccurate phenotype and CPIC recommendation.

  6. Nucleotide base calls are displayed on the positive chromosomal strand regardless of the gene strand; further information is provided under Gene-specific warnings in Section III: Allele Matching Details.

  7. Structural variation star alleles that cannot be detected using VCF file data:

    • CYP2B7-CYP2B6 hybrids: CYP2B6*29, CYP2B6*30
    • Partial and whole gene deletions: CYP2C19*36, CYP2C19*37, CYP4F2*16, SLCO1B1*48, SLCO1B1*49

  8. This report matches variants to genotypes assuming unphased data (unless phased data is provided in the VCF file and noted as such, see the relevant documentation for details). The assumption is that defined alleles exist in trans configuration, i.e. on opposite chromosomes, with exceptions noted in Section III: Allele Matching Details under "Gene-specific warnings." However, in cases where an allele is defined by a combination of two or more variants, where each variant alone also defines an allele, the match is based on the longer allele. For example, TPMT*3B is defined by one SNP, *3C is defined by another SNP, and *3A is defined by the combination of those two SNPs. In the case of unphased data that is heterozygous for both SNPs, the *1/*3A genotype is returned though the possibility of *3B/*3C cannot be ruled out.

    Below cases are summarized for which two calls with different scores are possible when provided unphased data and heterozygous calls for the variants that define the two alleles. The genotype with the higher score (longer allele) will be used to determine allele functionality, phenotype, and recommendation but the genotype with the lower score cannot be ruled out.

Table 1: Cases for which there is an overlap in the allele definitions.

Gene Genotype (Higher Score) Phenotype Genotype (Lower Score) Phenotype
UGT1A1 *1/*80+*28 Intermediate *28/*80 Indeterminate
UGT1A1 *1/*80+*37 Intermediate *37/*80 Indeterminate
TPMT *1/*3A Intermediate *3B/*3C Poor
NUDT15 *1/*2 Intermediate *3/*6 Possible Intermediate
CYP2C9 *1/*71 N/A *10/*22 Indeterminate
CYP2B6 *1/*36 Intermediate *6/*22 Intermediate
CYP2B6 *1/*34 Intermediate *33/*36 Indeterminate
CYP2B6 *1/*6 Intermediate *4/*9 Intermediate
CYP2B6 *1/*7 Intermediate *5/*6 Intermediate
CYP2B6 *1/*13 Intermediate *6/*8 Intermediate
SLCO1B1 *1/*46 Decreased function *15/*45 Possible Decreased Function
SLCO1B1 *1/*20 Normal Function *19/*37 Indeterminate
SLCO1B1 *1/*12 Indeterminate *2/*10 Indeterminate
SLCO1B1 *1/*13 Indeterminate *3/*11 Indeterminate
SLCO1B1 *1/*14 Normal Function *4/*37 Indeterminate
SLCO1B1 *1/*15 Decreased function *5/*37 Decreased function
SLCO1B1 *1/*25 Indeterminate *4/*28 Indeterminate
SLCO1B1 *1/*31 Decreased function *9/*37 Decreased Function
SLCO1B1 *1/*32 Indeterminate *4/*24 Indeterminate
SLCO1B1 *1/*40 Indeterminate *5/*19 Possible Decreased Function
SLCO1B1 *1/*43 Indeterminate *4/*44 Indeterminate
CYP4F2 *1/*4 N/A *2/*3 N/A
CYP3A4 *1/*37 N/A *3/*22 N/A
CYP3A4 *1/*38 N/A *3/*11 N/A
G6PD A- 202A_376G/B (reference) Variable A/Asahi Variable
G6PD B (reference)/Mt Sinai Variable A/Guadalajara Variable
G6PD B (reference)/Santa Maria Variable A/Malaga Variable
G6PD Ananindeua/B (reference) Variable A/Viangchan, Jammu Variable
G6PD B (reference)/Hechi Variable Asahi/Viangchan, Jammu Deficient
G6PD B (reference)/Hermoupolis Variable Cassano/Union,Maewo, Chinese-2, Kalo Deficient

Table 2: Cases for which there is an overlap in the allele definitions because the definition of the non-*1 allele in the genotype with the higher score allows for reference or variant at the position that defines the first allele listed in the genotype with the lower score. Both genotypes cannot be ruled out with unphased data if the position that overlaps between the respective alleles is heterozygous (0/1) in addition to heterozygous calls for the other variants that define the non-*1 allele in the genotype with the higher score.

Gene Genotype (Higher Score) Phenotype Genotype (Lower Score) Phenotype
CYP2C19 *1/*4 Intermediate *17/*4 Intermediate
CYP2C19 *1/*2 Intermediate *11/*2 Intermediate
CYP2C19 *1/*35 Intermediate *15/*35 Intermediate
CYP2B6 *1/*18 Intermediate *4/*18 Indeterminate

B. CPIC Allele Function, Phenotype and Recommendation

All content is sourced from the CPIC database.

C. DPWG Allele Function, Phenotype and Recommendation

  1. PharmGKB annotates PGx-based drug dosing guidelines published by the Royal Dutch Association for the Advancement of Pharmacy - Pharmacogenetics Working Group (DPWG). PharmGKB curates allele function assignments and phenotype mappings from the DPWG to provide genotype specific DPWG guideline recommendations. Where possible, PharmGKB maps DPWG terms to CPIC terms, as outlined on PharmGKB.

  2. CYP3A4 is currently not part of a CPIC guideline. Since the DPWG CYP3A4 documentation includes limit variant notations for the included alleles (only *16, *20, and *22 are specified). This report relies on PharmVar CYP3A4 allele definitions. However, the CYP3A4*16, *20 and *22 definitions are the same in both sources.

  3. The CPIC UGT1A1 allele definition file includes *6, *27, *28, *36, *37, and *80. Since the DPWG UGT1A1 document does not include allele definitions besides for the UGT1A1 TA box promoter polymorphism, this report only includes the UGT1A1 positions from the CPIC UGT1A1 allele definition file. Other UGT1A1 alleles can be supplied as outside calls but not be determined from the VCF file by the Named Allele Matcher.

D. FDA drug-label and Table of Pharmacogenetic Associations recommendations

This report includes recommendations from PharmGKB-annotated FDA drug labels and the FDA Table of Pharmacogenetic Associations. It only contains FDA information for genes with CPIC or DPWG guidelines because the FDA does not offer any genotype-to-phenotype mapping information. This report uses CPIC genotype-to-phenotype mappings when they exist, and DPWG genotype-to-phenotype mappings when no CPIC mappings exist, to determine the phenotypes to use with FDA label annotations and Table of Pharmacogenetic Associations entries. Results presented for FDA Table of Pharmacogenetic Associations use wording and “Affected Subgroups” taken directly from the Table. Results presented from PharmGKB-annotated drug labels present wording from the specific label that was curated. In many cases, multiple FDA labels may exist for a particular medication. Typically, PharmGKB annotates the label linked to from the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling but in some cases a different label may be annotated. Follow the “FDA Label Annotation” link in section II of the report to access the annotated label and more information.

E. Source Tags in Section II

Part of PharmGKB’s annotations of guidelines, drug labels and Table of Pharmacogenetic Associations is the assignment of labels that are meant to provide a high-level indication of the provided action. If recommendations or FDA Table wording exists, yellow boxes display if the guidance/wording is regarding (1) a dosing change, (2) recommending an alternate drug be used, or (3) other guidance. These boxes are included in the Source column in Section II of the report. More detailed information about what the yellow boxes mean is available on PharmGKB.

F. Exceptions to the CPIC Guideline Gene List

  1. This report does not determine CYP2D6, MT-RNR1, HLA-A, or HLA-B genotypes from the VCF file, but genotypes for CYP2D6, MT-RNR1, HLA-A, or HLA-B can be provided to this report from an outside source and the corresponding phenotype prescribing recommendations will be included in the generated report. For the required format of the outside calls refer to the outside calls documentation.

  2. CPIC has assigned function to the following CYP2D6 CNV alleles: *1x2, *1x≥3, *2x2, *2x≥3, *3x2, *4x2, *4x≥3, *6x2, *9x2, *10x2, *17x2, *29x2, *35x2, *36x2, *41x2, *41x3, *43x2, *45x2, *146x2. These alleles are part of the CPIC diplotype to phenotype translation and can be connected to recommendations. Other CNV notations from outside calls need to be mapped accordingly.

G. CPIC Guideline Disclaimers and Caveats

  1. A version of the following quoted disclaimer is part of each CPIC guideline and applies to the CPIC recommendations as used in this report. For the full description of potential benefits and risks, additional considerations (general and specific to gene-drug pairs), limitations, information about respective gene nomenclature systems, potential drug-drug interactions and clinical factors to consider, please see individual CPIC guidelines at (cpicpgx.org).

    1. "CPIC guidelines reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time a guideline was submitted for publication. Guidelines are limited in scope and are not applicable to interventions or diseases not specifically identified. Guidelines do not account for all individual variations among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guidelines is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. CPIC assumes no responsibility for any injury to persons or damage to persons or property arising out of or related to any use of CPIC's guidelines, or for any errors or omissions." (PMID: 27997040)

    2. "Caveats: appropriate use and/or potential misuse of genetic tests. The application of genotype-based dosing is most appropriate when initiating therapy with a tricyclic. Obtaining a pharmacogenetic test after months of drug therapy may be less helpful in some instances, as the drug dose may have already been adjusted based on plasma concentrations, response, or side effects. Similar to all diagnostic tests, genetic tests are one of several pieces of clinical information that should be considered before initiating drug therapy." (PMID: 27997040)

  2. CPIC guidelines reflect the alleles/genotypes known and considered by the guideline authors for inclusion by the time of publication, however they may be updated online at cpicpgx.org and in the CPIC database in between publications. Additional alleles and/or more extensive allele definitions might exist by the representative gene nomenclatures for various genes.

  3. CPIC is a registered service mark of the U.S. Department of Health & Human Services (HHS).

H. Disclaimers and Caveats

PharmGKB is a registered service mark of the U.S. Department of Health & Human Services (HHS).