PharmCAT Report

Titlepharmcat_positions
Date createdOctober 25, 2021
PharmCAT Versionv1.1.0-11-gfef2722
CPIC Versionv1.10
Disclaimer: PharmCAT 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 PharmCAT at their own risk. For a detailed disclaimer see section IV.

Sections

  1. Genotype Summary
  2. CPIC Recommendations
  3. Allele Matching Details
  4. Disclaimers

Genotype Summary

Genotypes called: 18 / 18

Drugs Gene Genotype Allele Functionality Phenotype Missing Variant Input*
CACNA1S
Reference/Reference
Two normal function alleles
Uncertain Susceptibility
No
CFTR
No CPIC variants found
Two ivacaftor non-responsive alleles
ivacaftor non-responsive in CF patients
No
CYP2B6
*1/*1
Two normal function alleles
Normal Metabolizer
No
CYP2C19
*38/*38
Two normal function alleles
Normal Metabolizer
No
CYP2C9
*1/*1
Two normal function alleles
Normal Metabolizer
No
CYP2D6
*1/*3
One no function allele and one normal function allele
Intermediate Metabolizer
N/A
CYP3A5
*1/*1
Two normal function alleles
Normal Metabolizer
No
CYP4F2
*1/*1
N/A
N/A
No
DPYD
Reference/Reference
Two normal function alleles
Normal Metabolizer
No
G6PD
B (wildtype)/B (wildtype)
Two normal function alleles
Normal
N/A
IFNL3/4
rs12979860 reference (C)/rs12979860 reference (C)
N/A
N/A
No
MT-RNR1
1555A>G
increased risk of aminoglycoside-induced hearing loss
increased risk of aminoglycoside-induced hearing loss
N/A
NUDT15
*1/*1
Two normal function alleles
Normal Metabolizer
No
RYR1
Reference/Reference
Two normal function alleles
Uncertain Susceptibility
No
SLCO1B1
*1/*1
Two normal function alleles
Normal function
No
TPMT
*1/*1
Two normal function alleles
Normal Metabolizer
No
UGT1A1
*1/*1
Two normal function alleles
Normal Metabolizer
No
VKORC1
rs9923231 reference (C)/rs9923231 reference (C)
N/A
N/A
No
* Indicates there are alleles not considered for the genotype calls due to missing variant information, please see Allele calls section. Alleles that could not be considered due to missing input might change the metabolizer phenotype and possible CPIC recommendation.
Check the allele call details for this gene for more details about this call.
PharmCAT 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.
For a full list of disclaimers and limitations see the Disclaimer section.

CPIC Recommendations

amikacin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

amitriptyline

CYP2C19: *38/*38 Two normal function alleles
CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
Implication for CYP2C19Normal metabolism of tertiary amines
Matched DiplotypesCYP2C19:*38/*38, CYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Phenotype for CYP2C19Normal Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationModerate
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

atazanavir

UGT1A1: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for UGT1A1Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir.
Matched DiplotypesUGT1A1:*1/*1
Phenotype for UGT1A1Normal Metabolizer
RecommendationThere is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient’s genotype makes this unlikely (less than about a 1 in 20 chance of stopping atazanavir because of jaundice).
Classification of RecommendationStrong
CommentsAll studies correlating UGT1A1 genotypes with atazanavir adverse events have involved ritonavir boosting. However, concentration-time profiles are equivalent when boosted with either cobicistat or ritonavir (PMID 23532097), and bilirubin-related adverse events including discontinuation of atazanavir occur in a similar percentage of patients prescribed atazanavir with cobicistat or ritonavir (PMID 23532097). Associations between UGT1A1 genotype, bilirubin elevations, and atazanavir/r discontinuation therefore almost certainly translate to atazanavir/cobicistat. "reference" function refers to the UGT1A1 allele to which other alleles are compared.

For more information read the guideline on cpicpgx.org.

Citations:

atomoxetine

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationpediatrics
Implication for CYP2D6Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInitiate with a dose of 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If < 200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL.
Classification of RecommendationModerate
CommentsTherapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL.
TypeAnnotation
Populationadults
Implication for CYP2D6Possibly higher atomoxetine concentrations as compared to normal metabolizers but questionable clinical significance. Intermediate metabolizers with an activity score of 1 may be at an increased risk of discontinuation as compared to poor metabolizers.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInitiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/mL, consider a proportional increase in dose to approach 400 ng/mL. Dosages greater than 100 mg/day may be needed to achieve target concentrations.
Classification of RecommendationModerate
CommentsTherapeutic range of 200 to 1000 ng/mL has been proposed (PMID 29493375). Limited data are available regarding the relationship between atomoxetine plasma concentrations and clinical response. Available information suggests that clinical response is greater in poor metabolizers (PMs) compared to non-PMs and may be related to the higher plasma concentrations 1 to 1.5 hours after dosing in PMs compared to non-PMs administered a similar dose. Furthermore, modest improvement in response, defined as reduction in ADHD-rating scale, is observed at peak concentrations greater than 400 ng/mL. Doses above 120 mg/day have not been evaluated.

For more information read the guideline on cpicpgx.org.

Citations:

azathioprine

NUDT15: *1/*1 Two normal function alleles
TPMT: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for TPMTLower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
Implication for NUDT15Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
Matched DiplotypesNUDT15:*1/*1, TPMT:*1/*1
Phenotype for TPMTNormal Metabolizer
Phenotype for NUDT15Normal Metabolizer
RecommendationStart with normal starting dose (e.g., 2-3 mg/kg/day) and adjust doses of azathioprine based on disease-specific guidelines. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11302950, 15606506).
Classification of RecommendationStrong
CommentsNormal 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.

For more information read the guideline on cpicpgx.org.

Citations:

capecitabine

DPYD: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for DPYDNormal DPD activity and "normal" risk for fluoropyrimidine toxicity
Matched DiplotypesDPYD:Reference/Reference
Phenotype for DPYDNormal Metabolizer
Activity Score for DPYD2.0
RecommendationBased on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

celecoxib

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

citalopram

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal metabolism
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate therapy with recommended starting dose
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

clomipramine

CYP2C19: *38/*38 Two normal function alleles
CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
Implication for CYP2C19Normal metabolism of tertiary amines
Matched DiplotypesCYP2C19:*38/*38, CYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Phenotype for CYP2C19Normal Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

clopidogrel

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal platelet inhibition; normal residual platelet aggregation
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationClopidogrel: label-recommended dosage and administration
Classification of RecommendationStrong
Antiplatelet therapy recommendations are based on CYP2C19 status when considering clopidogrel for acute coronary syndrome (ACS patients undergoing percutaneous coronary intervention (PCI)).

For more information read the guideline on cpicpgx.org.

Citations:

codeine

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced morphine formation
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61
RecommendationUse codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

desflurane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

desipramine

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

dexlansoprazole

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Classification of RecommendationOptional

For more information read the guideline on cpicpgx.org.

Citations:

doxepin

CYP2C19: *38/*38 Two normal function alleles
CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
Implication for CYP2C19Normal metabolism of tertiary amines
Matched DiplotypesCYP2C19:*38/*38, CYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Phenotype for CYP2C19Normal Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

efavirenz

CYP2B6: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationchild >40kg_adult
Implication for CYP2B6Normal efavirenz metabolism
Matched DiplotypesCYP2B6:*1/*1
Phenotype for CYP2B6Normal Metabolizer
RecommendationInitiate efavirenz with standard dosing (600 mg/day)
Classification of RecommendationStrong
CommentsThe 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).

For more information read the guideline on cpicpgx.org.

Citations:

enflurane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

escitalopram

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal metabolism
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate therapy with recommended starting dose
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

fluorouracil

DPYD: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for DPYDNormal DPD activity and "normal" risk for fluoropyrimidine toxicity
Matched DiplotypesDPYD:Reference/Reference
Phenotype for DPYDNormal Metabolizer
Activity Score for DPYD2.0
RecommendationBased on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

flurbiprofen

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

fluvoxamine

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInitiate therapy with recommended starting dose.
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

gentamicin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

halothane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

hydrocodone

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Minimal evidence for pharmacokinetic or clinical effect.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61
RecommendationUse hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.
Classification of RecommendationOptional

For more information read the guideline on cpicpgx.org.

Citations:

ibuprofen

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

imipramine

CYP2C19: *38/*38 Two normal function alleles
CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
Implication for CYP2C19Normal metabolism of tertiary amines
Matched DiplotypesCYP2C19:*38/*38, CYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Phenotype for CYP2C19Normal Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

isoflurane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

ivacaftor

CFTR: No CPIC variants found Two ivacaftor non-responsive alleles
TypeAnnotation
Populationgeneral
Implication for CFTRAn individual diagnosed with cystic fibrosis (CF) and negative for a CFTR variant listed in the FDA-approved drug label as being responsive to ivacaftor.
Matched DiplotypesCFTR:No CPIC variants found
Phenotype for CFTRivacaftor non-responsive in CF patients
RecommendationIvacaftor is not recommended
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

kanamycin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

lansoprazole

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

lornoxicam

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

meloxicam

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

mercaptopurine

NUDT15: *1/*1 Two normal function alleles
TPMT: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for TPMTLower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
Implication for NUDT15Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
Matched DiplotypesNUDT15:*1/*1, TPMT:*1/*1
Phenotype for TPMTNormal Metabolizer
Phenotype for NUDT15Normal Metabolizer
RecommendationStart with normal starting dose (e.g., 75 mg/m2/day or 1.5 mg/kg/day) and adjust doses of mercaptopurine (and of any other myelosuppressive therapy) without any special emphasis on mercaptopurine compared to other agents. Allow at least 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 16401827, 11302950).
Classification of RecommendationStrong
CommentsNormal 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.

For more information read the guideline on cpicpgx.org.

Citations:

methoxyflurane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

nortriptyline

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of tricyclic antidepressants to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of tricyclic antidepressants for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

omeprazole

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

ondansetron

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Very limited data available for CYP2D6 intermediate metabolizers
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInsufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.
Classification of RecommendationNo Recommendation
CommentsDrug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy.

For more information read the guideline on cpicpgx.org.

Citations:

pantoprazole

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate standard starting daily dose. Consider increasing dose by 50-100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

paromomycin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

paroxetine

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInitiate therapy with recommended starting dose
Classification of RecommendationModerate

For more information read the guideline on cpicpgx.org.

Citations:

peginterferon alfa-2a

No CPIC recommendation for this allele combination.

For more information read the guideline on cpicpgx.org.

Citations:

peginterferon alfa-2b

No CPIC recommendation for this allele combination.

For more information read the guideline on cpicpgx.org.

Citations:

piroxicam

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

plazomicin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

rasburicase

G6PD: B (wildtype)/B (wildtype) Two normal function alleles (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for G6PDLow or reduced risk of hemolytic anemia
Matched DiplotypesG6PD:B (wildtype)/B (wildtype)
Phenotype for G6PDNormal
RecommendationNo reason to withhold rasburicase based on G6PD status.
Classification of RecommendationStrong
CommentsA negative or inconclusive genetic test cannot be assumed to indicate normal G6PD phenotype; an enzyme actiity test is needed to assign G6PD phenotype in such cases.

For more information read the guideline on cpicpgx.org.

Citations:

sertraline

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for CYP2C19Normal metabolism
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate therapy with recommended starting dose
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

sevoflurane

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

simvastatin

SLCO1B1: *1/*1 Two normal function alleles
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 *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for SLCO1B1Normal myopathy risk
Matched DiplotypesSLCO1B1:*1/*1
Phenotype for SLCO1B1Normal function
RecommendationPrescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines
Classification of RecommendationStrong
CommentsIn all cases, the potential for drug-drug interactions should be evaluated before initiating a prescription. The US Food and Drug Administration recommends against 80 mg (unless already tolerated for 12 months).

For more information read the guideline on cpicpgx.org.

Citations:

streptomycin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

succinylcholine

CACNA1S: Reference/Reference Two normal function alleles
RYR1: Reference/Reference Two normal function alleles
TypeAnnotation
Populationgeneral
Implication for RYR1These results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Implication for CACNA1SThese results do not eliminate the chance that this patient is susceptible to malignant hyperthermia (MH). The genetic cause of about half of all MH survivors, with MH susceptibility confirmed by contracture test, remains unknown (PMID 28902675).
Matched DiplotypesCACNA1S:Reference/Reference, RYR1:Reference/Reference
Phenotype for RYR1Uncertain Susceptibility
Phenotype for CACNA1SUncertain Susceptibility
RecommendationClinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

tacrolimus

CYP3A5: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP3A5Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations.
Matched DiplotypesCYP3A5:*1/*1
Phenotype for CYP3A5Normal Metabolizer
RecommendationIncrease starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3 mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationStrong
CommentsThis recommendation includes the use of tacrolimus in kidney, heart, lung and hematopoietic stem cell transplant patients, and liver transplant patients where the donor and recipient genotypes are identical. Further dose adjustments or selection of alternative therapy may be necessary due to other clinical factors (e.g., medication interactions, or hepatic function). Typically with other CYP enzymes, a normal metabolizer would be classified as having normal metabolism, and therefore, the drug dose would not change based on the patient’s genotype. However, in the case of CYP3A5 and tacrolimus, a CYP3A5 expresser (i.e., CYP3A5 normal metabolizer or intermediate metabolizer) would require a higher recommended starting dose, and the CYP3A5 non-expresser (i.e., poor metabolizer) would require the standard recommended starting dose.

For more information read the guideline on cpicpgx.org.

Citations:

tamoxifen

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers.
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype (PMID 26211827). If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day)(PMID 27226358). Avoid CYP2D6 strong to weak inhibitors.
Classification of RecommendationOptional

For more information read the guideline on cpicpgx.org.

Citations:

tenoxicam

CYP2C9: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2C9Normal metabolism
Matched DiplotypesCYP2C9:*1/*1
Phenotype for CYP2C9Normal Metabolizer
Activity Score for CYP2C92.0
RecommendationInitiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for shortest duration consistent with individual patient treatment goals.
Classification of RecommendationStrong

For more information read the guideline on cpicpgx.org.

Citations:

thioguanine

NUDT15: *1/*1 Two normal function alleles
TPMT: *1/*1 Two normal function alleles
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for TPMTLower concentrations of TGN metabolites, but note that TGN after thioguanine are 5-10X higher than TGN after mercaptopurine or azathioprine. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression.
Implication for NUDT15Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression
Matched DiplotypesNUDT15:*1/*1, TPMT:*1/*1
Phenotype for TPMTNormal Metabolizer
Phenotype for NUDT15Normal Metabolizer
RecommendationStart with normal starting dose (e.g., 40-60 mg/m2/day) and adjust doses of thioguanine and of other myelosuppressive therapy without any special emphasis on thioguanine. Allow 2 weeks to reach steady-state after each dose adjustment (PMID 20354201, 11037857).
Classification of RecommendationStrong
CommentsNormal 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.

For more information read the guideline on cpicpgx.org.

Citations:

tobramycin

MT-RNR1: 1555A>G increased risk of aminoglycoside-induced hearing loss (from Outside Call)
TypeAnnotation
Populationgeneral
Implication for MT-RNR1Very high risk of developing hearing loss if administered an aminoglycoside antibiotic.
Matched DiplotypesMT-RNR1:1555A>G
Phenotype for MT-RNR1increased risk of aminoglycoside-induced hearing loss
RecommendationAvoid aminoglycoside anitbiotics unless the high risk of permanent hearing loss is outweighed by the severity of infection and lack of safe or effective alternative therapies.
Classification of RecommendationStrong
CommentsIf no effective alternative to an aminoglycoside antibiotic is available, evaluate for hearing loss frequently during therapy and ensure that all appropriate precautions are utilized (e.g., lowest possible dose and duration, utilization of therapeutic drug monitoring, hydration, renal function monitoring).

For more information read the guideline on cpicpgx.org.

Citations:

tramadol

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced O-desmethyltramadol (active metabolite) formation
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61
RecommendationUse tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.
Classification of RecommendationOptional

For more information read the guideline on cpicpgx.org.

Citations:

trimipramine

CYP2C19: *38/*38 Two normal function alleles
CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Reduced metabolism of TCAs to less active compounds compared to normal metabolizers; Higher plasma concentrations of active drug will increase the probability of side effects
Implication for CYP2C19Normal metabolism of tertiary amines
Matched DiplotypesCYP2C19:*38/*38, CYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Phenotype for CYP2C19Normal Metabolizer
Activity Score for CYP2D61.0
RecommendationConsider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.
Classification of RecommendationOptional
CommentsPatients 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. Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

For more information read the guideline on cpicpgx.org.

Citations:

tropisetron

CYP2D6: *1/*3 One no function allele and one normal function allele (from Outside Call)
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
TypeAnnotation
Populationgeneral
Implication for CYP2D6Very limited data available for CYP2D6 intermediate metabolizers
Matched DiplotypesCYP2D6:*1/*3
Phenotype for CYP2D6Intermediate Metabolizer
Activity Score for CYP2D61.0
RecommendationInsufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.
Classification of RecommendationNo Recommendation
CommentsDrug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy.

For more information read the guideline on cpicpgx.org.

Citations:

voriconazole

CYP2C19: *38/*38 Two normal function alleles
TypeAnnotation
Populationpediatrics
Implication for CYP2C19Normal voriconazole metabolism
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate therapy with recommended standard of care dosing
Classification of RecommendationStrong
CommentsFurther 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.
TypeAnnotation
Populationadults
Implication for CYP2C19Normal voriconazole metabolism
Matched DiplotypesCYP2C19:*38/*38
Phenotype for CYP2C19Normal Metabolizer
RecommendationInitiate therapy with recommended standard of care dosing
Classification of RecommendationStrong
CommentsFurther 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.

For more information read the guideline on cpicpgx.org.

Citations:

warfarin

CYP2C9: *1/*1 Two normal function alleles
Please follow the flow chart in figure 2 of the CPIC warfarin guideline to determine the appropriate dosing recommendation.
The *1 allele assignment is characterized by the absence of variants that are included in the underlying allele definitions by either position being reference or missing.
Figure 2 from the CPIC guideline for warfarin
The CPIC warfarin guideline only considers a single SNV in VKORC1 (rs9923231), which is found in the highest frequency in Caucasians and extremely low frequency in those of African descent. While other functional variants in VKORC1 have been observed in much higher frequencies in some populations, 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).

For more information read the guideline on cpicpgx.org.

Citations:

Allele Matching Details

  1. CACNA1S allele match data
  2. CFTR allele match data
  3. CYP2B6 allele match data
  4. CYP2C19 allele match data
  5. CYP2C9 allele match data
  6. CYP2D6 allele match data
  7. CYP3A5 allele match data
  8. CYP4F2 allele match data
  9. DPYD allele match data
  10. G6PD allele match data
  11. IFNL3/4 allele match data
  12. MT-RNR1 allele match data
  13. NUDT15 allele match data
  14. RYR1 allele match data
  15. SLCO1B1 allele match data
  16. TPMT allele match data
  17. UGT1A1 allele match data
  18. VKORC1 allele match data

CACNA1S allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr1:201060815 rs1800559 C|C C c.3257G>A
chr1:201091993 rs772226819 G|G G c.520C>T

CFTR allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr7:117509035 rs397508256 G|G G E56K
chr7:117509069 rs368505753 C|C C P67L
chr7:117509089 rs115545701 C|C C R74W
chr7:117530953 rs113993958 G|G G D110H
chr7:117530955 rs397508537 C|C C D110E
chr7:117530974 rs77834169 C|C C R117C
chr7:117530975 rs78655421 G|G G R117H
chr7:117534318 rs80282562 G|G G G178R
chr7:117534363 rs397508759 G|G G E193K
chr7:117534368 rs397508761 A|A A 711+3A->G
chr7:117535285 rs121908752 T|T T L206W
chr7:117540270 rs77932196 G|G G R347H
chr7:117540285 rs121908753 G|G G R352Q
chr7:117548795 rs74551128 C|C C A455E
chr7:117587799 rs121908757 A|A A S549R(A>C)
chr7:117587800 rs121908755 G|G G S549N
chr7:117587801 rs121909005 T|T T S549R(T>G)
chr7:117587805 rs121909013 G|G G G551S
chr7:117587806 rs75527207 G|G G G551D
chr7:117590409 rs397508288 A|A A D579G
chr7:117594930 rs397508387 G|G G E831X
chr7:117602868 rs80224560 G|G G 2789+5G->A
chr7:117603708 rs397508442 C|C C S945L
chr7:117606695 rs141033578 C|C C S977F
chr7:117611555 rs76151804 A|A A 3272-26A->G
chr7:117611595 rs150212784 T|T T F1052V
chr7:117611620 rs397508513 A|A A K1060T
chr7:117611640 rs121909020 G|G G A1067T
chr7:117611646 rs200321110 G|G G G1069R
chr7:117611649 rs202179988 C|C C R1070W
chr7:117611650 rs78769542 G|G G R1070Q
chr7:117611663 rs186045772 T|T T F1074L
chr7:117614699 rs75541969 G|G G D1152H
chr7:117639961 rs75039782 C|C C 3849+10kbC->T
chr7:117642451 rs267606723 G|G G G1244E
chr7:117642472 rs74503330 G|G G S1251N
chr7:117642483 rs121909041 T|T T S1255P
chr7:117642528 rs11971167 G|G G D1270N
chr7:117664770 rs193922525 G|G G G1349D

CYP2B6 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr19:40991224 rs34223104 T|T T *22 *34 *35 *36
chr19:40991367 rs34883432 A|A A *10
chr19:40991369 rs8192709 C|C C *2 *10
chr19:40991381 rs33973337 A|A A *17
chr19:40991388 rs33980385 A|A A *17
chr19:40991390 rs33926104 C|C C *17
chr19:40991391 rs34284776 G|G G *17
chr19:40991441 rs35303484 A|A A *11
chr19:41004015 rs281864907 T|T T *38
chr19:41004125 rs36060847 G|G G *12
chr19:41004158 rs186335453 G|G G *35
chr19:41004303 rs139801276 T|T T *35
chr19:41004377 rs12721655 A|A A *8 *13
chr19:41004381 rs35773040 G|G G *14
chr19:41004406 rs145884402 G|G G *35
chr19:41006919 rs3826711 C|C C *26
chr19:41006923 rs36056539 C|C C *20
chr19:41006936 rs3745274 G|G G *6 *7 *9 *13 *19 *20 *26 *34 *36 *37 *38
chr19:41006968 rs373489637 T|T T *37
chr19:41007013 rs36079186 T|T T *27 *35
chr19:41009350 rs45482602 C|C C *3
chr19:41009358 rs2279343 A|A A *4 *6 *7 *13 *18 *19 *20 *26 *34 *36 *37 *38
chr19:41010006 rs139029625 G|G G *35
chr19:41010088 rs34698757 C|C C *28
chr19:41010108 rs193922917 C|C C *31
chr19:41012316 rs28399499 T|T T *18
chr19:41012339 rs34826503 C|C C *19
chr19:41012465 rs34097093 C|C C *28
chr19:41012693 rs35979566 T|T T *15
chr19:41012740 rs193922918 G|G G *32
chr19:41012803 rs35010098 C|C C *21
chr19:41016726 rs3211369 A|A A *23
chr19:41016778 rs564083989 G|G G *24
chr19:41016805 A|A A *25
chr19:41016810 rs3211371 C|C C *5 *7 *33 *34

CYP2C19 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr10:94761900 rs12248560 C|C C *4 *17
chr10:94762706 rs28399504 A|A A *4
chr10:94762712 rs367543002 C|C C *34
chr10:94762715 rs367543003 T|T T *34
chr10:94762755 rs55752064 T|T T *14
chr10:94762760 rs17882687 A|A A *15 *28 *35 *39
chr10:94762788 rs1564656981 A|A A *29
chr10:94762856 rs1564657013 A|A A *19
chr10:94775106 rs145328984 C|C C *30
chr10:94775121 rs1564660997 C|C C *31
chr10:94775160 rs118203756 G|G G *23
chr10:94775185 rs1288601658 A|A A *32
chr10:94775367 rs12769205 A|A A *2 *35
chr10:94775416 rs41291556 T|T T *8
chr10:94775423 rs17885179 A|A A *39
chr10:94775453 rs72552267 G|G G *6
chr10:94775489 rs17884712 G|G G *9
chr10:94775507 rs58973490 G|G G *2 *11
chr10:94780574 rs140278421 G|G G *22
chr10:94780579 rs370803989 G|G G *33
chr10:94780653 rs4986893 G|G G *3
chr10:94781858 rs6413438 C|C C *10
chr10:94781859 rs4244285 G|G G *2
chr10:94781944 rs375781227 G|G G *26
chr10:94781999 rs72558186 T|T T *7
chr10:94842861 rs138142612 G|G G *18
chr10:94842866 rs3758581 A|A A *2 *3 *4 *5 *6 *8 *9 *10 *11 *12 *13 *14 *15 *17 *18 *19 *22 *23 *24 *25 *26 *28 *29 *31 *32 *33 *35 *39
chr10:94842879 rs118203757 G|G G *24
chr10:94842995 rs113934938 G|G G *28
chr10:94849995 rs17879685 C|C C *13
chr10:94852738 rs56337013 C|C C *5
chr10:94852765 rs192154563 C|C C *16
chr10:94852785 rs118203759 C|C C *25
chr10:94852914 rs55640102 A|A A *12

CYP2C9 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr10:94938683 rs114071557 A|A A *36
chr10:94938737 rs67807361 C|C C *7
chr10:94938771 rs142240658 C|C C *21
chr10:94938803 rs2031308986 A|A A *22
chr10:94938828 rs564813580 A|A A *37
chr10:94941897 rs371055887 G|G G *20
chr10:94941915 G|G G *23
chr10:94941958 rs72558187 T|T T *13
chr10:94941976 G|G G *38
chr10:94941982 rs762239445 G|G G *39
chr10:94942018 T|T T *40
chr10:94942205 rs1304490498 CAATGGAAAGA|CAATGGAAAGA CAATGGAAAGA *25
chr10:94942216 rs774607211 A|A A *41
chr10:94942230 rs767576260 C|C C *43
chr10:94942231 rs12414460 G|G G *42
chr10:94942233 rs375805362 C|C C *62
chr10:94942234 rs72558189 G|G G *14 *35
chr10:94942249 rs200965026 C|C C *26 *44
chr10:94942254 rs199523631 C|C C *45
chr10:94942255 rs200183364 G|G G *33
chr10:94942290 rs1799853 C|C C *2 *35 *61
chr10:94942291 rs141489852 G|G G *63
chr10:94942305 rs754487195 G|G G *46
chr10:94942309 rs7900194 G|G G *8 *27
chr10:94947782 rs72558190 C|C C *15
chr10:94947785 rs774550549 C|C C *47
chr10:94947869 A|A A *69
chr10:94947907 A|A A *57
chr10:94947917 rs1326630788 T|T T *48
chr10:94947938 rs2031531005 A|A A *28
chr10:94949129 A|A A *49
chr10:94949144 C|C C *50
chr10:94949217 rs2256871 A|A A *9
chr10:94949280 rs9332130 A|A A *10 *71
chr10:94949281 rs9332131 GA|GA GA *6
chr10:94972119 rs182132442 C|C C *29
chr10:94972123 C|C C *64
chr10:94972134 A|A A *51
chr10:94972179 rs72558192 A|A A *16
chr10:94972180 rs988617574 C|C C *52
chr10:94972233 rs1237225311 C|C C *53
chr10:94981199 G|G G *65
chr10:94981201 rs57505750 T|T T *31
chr10:94981224 rs28371685 C|C C *11
chr10:94981225 rs367826293 G|G G *34
chr10:94981230 rs1274535931 C|C C *58
chr10:94981250 rs750820937 C|C C *54
chr10:94981281 rs749060448 G|G G *24
chr10:94981296 rs1057910 A|A A *3 *18 *68
chr10:94981297 rs56165452 T|T T *4
chr10:94981301 rs28371686 C|C C *5
chr10:94981302 rs1250577724 C|C C *55
chr10:94981305 rs578144976 C|C C *66
chr10:94981365 C|C C *17
chr10:94981371 rs542577750 G|G G *68
chr10:94986042 rs764211126 A|A A *56
chr10:94986073 rs72558193 A|A A *18
chr10:94988852 rs776908257 C|C C *67
chr10:94988855 A|A A *59
chr10:94988880 G|G G *70
chr10:94988917 rs769942899 G|G G *19
chr10:94988925 rs202201137 A|A A *61
chr10:94988955 rs767284820 T|T T *60
chr10:94988984 rs781583846 G|G G *30
chr10:94989020 rs9332239 C|C C *12 *71
chr10:94989023 rs868182778 G|G G *32

Other Positions of Interest

Position in VCF RSID Call in VCF
chr10:94645745 rs12777823 G|G

CYP2D6 allele match data

Genotype reported

Phasing status: Unavailable for calls made outside PharmCAT

The call for CYP2D6 comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
No variant data available.
CYP2D6 genotypes are called by a separate algorithm from other genes in the PharmCAT report. Please refer to the PharmCAT wiki for more information.

CYP3A5 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr7:99652613 rs28365083 G|G G *2 *3
chr7:99652770 rs41303343 T|T T *7
chr7:99660516 rs28383479 C|C C *3 *9
chr7:99665212 rs10264272 C|C C *6
chr7:99665237 rs56411402 T|T T *3 *4
chr7:99666950 rs55965422 A|A A *3 *5
chr7:99672916 rs776746 T|T T *3
chr7:99676198 rs55817950 G|G G *8

CYP4F2 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr19:15879621 rs2108622 C|C C *3
chr19:15897578 rs3093105 A|A A *2

DPYD allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr1:97078987 rs114096998 G|G G c.3067C>A
chr1:97078993 rs148799944 C|C C c.3061G>C
chr1:97079005 rs140114515 C|C C c.3049G>A
chr1:97079071 rs1801268 C|C C c.2983G>T (*10)
chr1:97079076 rs139459586 A|A A c.2978T>G
chr1:97079077 rs202144771 G|G G c.2977C>T
chr1:97079121 rs72547601 T|T T c.2933A>G
chr1:97079133 rs72547602 T|T T c.2921A>T
chr1:97079139 rs145529148 T|T T c.2915A>G
chr1:97082365 rs141044036 T|T T c.2872A>G
chr1:97082391 rs67376798 T|T T c.2846A>T
chr1:97098598 rs1801267 C|C C c.2657G>A (*9B)
chr1:97098599 rs147545709 G|G G c.2656C>T
chr1:97098616 rs55674432 C|C C c.2639G>T
chr1:97098632 rs201035051 T|T T c.2623A>C
chr1:97193109 rs60139309 T|T T c.2582A>G
chr1:97193209 rs200687447 C|C C c.2482G>A
chr1:97234958 rs199634007 G|G G c.2336C>A
chr1:97234991 rs56005131 G|G G c.2303C>A
chr1:97305279 rs112766203 G|G G c.2279C>T
chr1:97305363 rs60511679 A|A A c.2195T>G
chr1:97305364 rs1801160 C|C C c.2194G>A (*6)
chr1:97305372 rs146529561 G|G G c.2186C>T
chr1:97306195 rs145548112 C|C C c.2161G>A
chr1:97373598 rs137999090 C|C C c.2021G>A
chr1:97373629 rs138545885 C|C C c.1990G>T
chr1:97382461 rs55971861 T|T T c.1906A>C
chr1:97450058 rs3918290 C|C C c.1905+1G>A (*2A)
chr1:97450059 rs3918289 G|G G c.1905C>G
chr1:97450065 rs72549303 TG|TG TG c.1898delC (*3)
chr1:97450068 rs17376848 A|A A c.1896T>C
chr1:97450168 rs147601618 A|A A c.1796T>C
chr1:97450187 rs145773863 C|C C c.1777G>A
chr1:97450189 rs138616379 C|C C c.1775G>A
chr1:97450190 rs59086055 G|G G c.1774C>T
chr1:97515784 rs201615754 C|C C c.1682G>T
chr1:97515787 rs55886062 A|A A c.1679T>G (*13)
chr1:97515839 rs1801159 T|T T c.1627A>G (*5)
chr1:97515851 rs142619737 C|C C c.1615G>A
chr1:97515865 rs1801158 C|C C c.1601G>A (*4)
chr1:97515889 rs190951787 G|G G c.1577C>G
chr1:97515923 rs148994843 C|C C c.1543G>A
chr1:97549565 rs138391898 C|C C c.1519G>A
chr1:97549600 rs111858276 T|T T c.1484A>G
chr1:97549609 rs72549304 G|G G c.1475C>T
chr1:97549681 rs199549923 G|G G c.1403C>A
chr1:97549713 rs57918000 G|G G c.1371C>T
chr1:97549726 rs144395748 G|G G c.1358C>G
chr1:97549735 rs72975710 G|G G c.1349C>T
chr1:97573785 rs186169810 A|A A c.1314T>G
chr1:97573805 rs142512579 C|C C c.1294G>A
chr1:97573821 rs764666241 C|C C c.1278G>T
chr1:97573839 rs200064537 A|A A c.1260T>A
chr1:97573863 rs56038477 C|C C c.1129-5923C>G, c.1236G>A (HapB3)
chr1:97573881 rs61622928 C|C C c.1218G>A
chr1:97573918 rs143815742 C|C C c.1181G>T
chr1:97573919 rs140602333 G|G G c.1180C>T
chr1:97573943 rs78060119 C|C C c.1156G>T (*12)
chr1:97579893 rs75017182 G|G G c.1129-5923C>G, c.1236G>A (HapB3)
chr1:97593238 rs72549305 T|T T c.1108A>G
chr1:97593289 rs143154602 G|G G c.1057C>T
chr1:97593322 rs183385770 C|C C c.1024G>A
chr1:97593343 rs72549306 C|C C c.1003G>T (*11)
chr1:97593379 rs201018345 C|C C c.967G>A
chr1:97595083 rs145112791 G|G G c.934C>T
chr1:97595088 rs150437414 A|A A c.929T>C
chr1:97595149 rs146356975 T|T T c.868A>G
chr1:97679170 rs45589337 T|T T c.775A>G
chr1:97691776 rs1801266 G|G G c.703C>T (*8)
chr1:97699399 rs72549307 T|T T c.632A>G
chr1:97699430 rs72549308 T|T T c.601A>C
chr1:97699474 rs115232898 T|T T c.557A>G
chr1:97699506 rs6670886 C|C C c.525G>A
chr1:97699533 rs139834141 C|C C c.498G>A
chr1:97699535 rs2297595 T|T T c.496A>G
chr1:97721542 rs200562975 T|T T c.451A>G
chr1:97721650 rs141462178 T|T T c.343A>G
chr1:97740400 rs150385342 C|C C c.313G>A
chr1:97740410 rs72549309 GATGA|GATGA GATGA c.295_298delTCAT (*7)
chr1:97883329 rs1801265 A|A A c.85T>C (*9A)
chr1:97883352 rs80081766 C|C C c.62G>A
chr1:97883353 rs72549310 G|G G c.61C>T
chr1:97883368 rs150036960 G|G G c.46C>G

G6PD allele match data

Genotype reported

Phasing status: Unavailable for calls made outside PharmCAT

The call for G6PD comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
No variant data available.

IFNL3/4 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr19:39248147 rs12979860 C|C C rs12979860 variant (T)

MT-RNR1 allele match data

Genotype reported

Phasing status: Unavailable for calls made outside PharmCAT

The call for MT-RNR1 comes from an outside data source which does not supply position-level detail. For specific disclaimers and limitations, see the original genotyping source.
No variant data available.

NUDT15 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr13:48037748 rs769369441 T|T T *10
chr13:48037749 G|G G *19
chr13:48037782 rs746071566 AGGAGTC|AGGAGTC AGGAGTC *2 *6 *9
chr13:48037798 rs186364861 G|G G *5
chr13:48037825 rs777311140 C|C C *14
chr13:48037834 rs1202487323 C|C C *16
chr13:48037847 rs766023281 G|G G *7
chr13:48037849 A|A A *8
chr13:48037885 rs1950545307 G|G G *11
chr13:48037902 rs149436418 C|C C *12
chr13:48040977 rs1457579126 GA|GA GA *18
chr13:48041103 rs761191455 T|T T *13
chr13:48041113 rs1368252918 G|G G *17
chr13:48045690 rs768324690 C|C C *20
chr13:48045719 rs116855232 C|C C *2 *3
chr13:48045720 rs147390019 G|G G *4
chr13:48045771 rs139551410 T|T T *15

RYR1 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr19:38440802 rs193922747 T|T T c.103T>C
chr19:38440829 rs193922748 C|C C c.130C>T
chr19:38444211 rs118192161 C|C C c.487C>T
chr19:38444212 rs193922753 G|G G c.488G>T
chr19:38446710 rs1801086 G|G G c.742G>A c.742G>C
chr19:38448673 rs193922762 C|C C c.982C>T
chr19:38448712 rs121918592 G|G G c.1021G>A c.1021G>C
chr19:38451842 rs193922764 C|C C c.1201C>T
chr19:38451850 rs118192116 C|C C c.1209C>G
chr19:38455359 rs118192162 A|A A c.1565A>C
chr19:38455463 rs111888148 G|G G c.1589G>A
chr19:38455471 rs193922768 C|C C c.1597C>T
chr19:38455472 rs144336148 G|G G c.1598G>A
chr19:38455528 rs193922770 C|C C c.1654C>T
chr19:38457545 rs118192172 C|C C c.1840C>T
chr19:38457546 rs193922772 G|G G c.1841G>T
chr19:38494564 rs118192175 C|C C c.6487C>T
chr19:38494565 rs118192163 G|G G c.6488G>A
chr19:38494579 rs118192176 G|G G c.6502G>A
chr19:38496283 rs118192177 C|C C c.6617C>G c.6617C>T
chr19:38499223 rs112563513 G|G G c.7007G>A
chr19:38499644 rs121918596 TGGA|TGGA TGGA c.7042_7044delGAG
chr19:38499655 rs193922802 G|G G c.7048G>A
chr19:38499670 rs193922803 C|C C c.7063C>T
chr19:38499731 rs193922807 G|G G c.7124G>C
chr19:38499975 rs193922809 G|G G c.7282G>A
chr19:38499993 rs121918593 G|G G c.7300G>A
chr19:38499997 rs28933396 G|G G c.7304G>A
chr19:38500636 rs118192124 C|C C c.7354C>T
chr19:38500642 rs193922816 C|C C c.7360C>T
chr19:38500643 rs118192122 G|G G c.7361G>A
chr19:38500654 rs28933397 C|C C c.7372C>T
chr19:38500655 rs121918594 G|G G c.7373G>A
chr19:38500898 rs118192178 C|C C c.7522C>G c.7522C>T
chr19:38500899 rs193922818 G|G G c.7523G>A
chr19:38512321 rs193922832 G|G G c.9310G>A
chr19:38543832 rs193922843 G|G G c.11969G>T
chr19:38580004 rs118192167 A|A A c.14387A>G
chr19:38580094 rs121918595 C|C C c.14477C>T
chr19:38580114 rs193922876 C|C C c.14497C>T
chr19:38580370 rs193922878 C|C C c.14512C>G
chr19:38580403 rs118192168 G|G G c.14545G>A
chr19:38580440 rs63749869 G|G G c.14582G>A
chr19:38584989 rs118192170 T|T T c.14693T>C

SLCO1B1 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr12:21172734 rs139257324 C|C C *33
chr12:21172776 rs373327528 G|G G *23
chr12:21172782 rs56101265 T|T T *2 *12
chr12:21174595 rs56061388 T|T T *3 *13
chr12:21176804 rs2306283 A|A A *14 *15 *20 *24 *25 *27 *28 *29 *30 *31 *32 *33 *37 *39 *42 *43 *44 *46 *47
chr12:21176868 rs2306282 A|A A *16
chr12:21176871 G|G G *38
chr12:21176879 rs11045819 C|C C *4 *14 *25 *32 *43
chr12:21176883 rs72559745 A|A A *3 *13
chr12:21176898 rs77271279 G|G G *41
chr12:21178612 rs141467543 A|A A *42
chr12:21178615 rs4149056 T|T T *5 *15 *40 *46 *47
chr12:21178957 rs79135870 A|A A *30
chr12:21196951 rs11045852 A|A A *24 *25 *28 *32 *33 *43 *44
chr12:21196975 rs183501729 C|C C *39
chr12:21196976 rs11045853 G|G G *25 *28 *33
chr12:21200544 rs72559747 C|C C *47
chr12:21200595 rs55901008 T|T T *6
chr12:21202553 rs1228465562 T|T T *36
chr12:21202555 rs59113707 C|C C *27
chr12:21202649 rs56387224 A|A A *7
chr12:21202664 rs142965323 G|G G *26
chr12:21205921 rs72559748 A|A A *8
chr12:21205999 rs59502379 G|G G *9 *31
chr12:21206031 rs74064213 A|A A *43 *44
chr12:21222355 rs71581941 C|C C *45 *46
chr12:21239042 rs34671512 A|A A *19 *20 *40
chr12:21239077 rs56199088 A|A A *10 *12
chr12:21239113 rs55737008 A|A A *11 *13
chr12:21239145 rs200995543 C|C C *34
chr12:21239158 rs140790673 C|C C *29

TPMT allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr6:18130687 rs1142345 T|T T *3A *3C *41
chr6:18130694 rs150900439 T|T T *20
chr6:18130725 rs72552736 A|A A *7
chr6:18130729 rs139392616 C|C C *40
chr6:18130758 rs398122996 A|A A *37
chr6:18130762 rs56161402 C|C C *8
chr6:18130772 rs377085266 A|A A *25
chr6:18130781 rs1800584 C|C C *4
chr6:18132136 rs72556347 A|A A *26
chr6:18132147 rs79901429 A|A A *31
chr6:18132163 C|C C *36
chr6:18133845 rs75543815 T|T T *6
chr6:18133847 rs6921269 C|C C *24
chr6:18133870 rs772832951 A|A A *38
chr6:18133884 rs74423290 G|G G *23
chr6:18133887 rs201695576 T|T T *44
chr6:18133890 rs9333570 C|C C *15
chr6:18138969 rs144041067 C|C C *16 *22
chr6:18138970 rs112339338 G|G G *33
chr6:18138997 rs1800460 C|C C *3A *3B
chr6:18139027 rs72552737 C|C C *10
chr6:18139689 rs72552738 C|C C *11
chr6:18139710 rs200220210 G|G G *12
chr6:18143597 T|T T *19
chr6:18143606 rs151149760 T|T T *9
chr6:18143613 C|C C *28
chr6:18143622 rs115106679 C|C C *32
chr6:18143643 A|A A *27
chr6:18143700 rs753545734 C|C C *43
chr6:18143718 rs111901354 G|G G *34
chr6:18143724 rs1800462 C|C C *2
chr6:18143728 rs1256618794 C|C C *43
chr6:18147838 rs281874771 G|G G *39
chr6:18147845 rs777686348 C|C C *18
chr6:18147851 rs200591577 G|G G *21
chr6:18147856 A|A A *35
chr6:18147910 rs72552740 A|A A *5
chr6:18149004 G|G G *17
chr6:18149022 rs750424422 C|C C *30
chr6:18149032 rs759836180 C|C C *42
chr6:18149045 rs72552742 T|T T *13
chr6:18149126 rs267607275 A|A A *29
chr6:18149127 rs9333569 T|T T *14

UGT1A1 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr2:233759924 rs887829 C|C C *80 *80+*28 *80+*37
chr2:233760233 rs3064744 CAT|CAT CAT *28 *36 *37 *80+*28 *80+*37
chr2:233760498 rs4148323 G|G G *6
chr2:233760973 rs35350960 C|C C *27

VKORC1 allele match data

Genotype matched

Phasing status: Phased

Calls at Positions

Position in VCF RSID Call in VCF Reference Related Alleles
chr16:31096368 rs9923231 C|C C rs9923231 variant (T)

Disclaimers and Other Information

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

A. Allele and Genotype Determination

  1. PharmCAT uses gene allele definitions included in the CPIC database, with exceptions as noted in Gene Definition Exceptions document. For allele definitions and the positions used in PharmCAT, see the gene definition tables.

  2. PharmCAT results are dependent on the supplied vcf calls for the queried positions (for technical information about PharmCAT input formatting and requirements, please go to pharmcat.org). PharmCAT 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. See the gene definition tables for more information about what positions are queried in the vcf file. Missing positions might alter the assigned genotype, subsequent phenotype prediction and CPIC recommendation. If the supplied vcf file is missing positions, those positions will be noted in Section 3: Allele Calls 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.

  3. 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.

  4. 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, similar to the situation in point 3, above.

  5. 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 3: Allele Calls.

  6. PharmCAT matches variants to genotypes assuming unphased data (unless phased data is provided in the vcf file and noted as such, see pharmcat.org for details). The assumption is that defined alleles exist in trans configuration, i.e. on opposite chromosomes, with exceptions noted in Section 3: Allele Calls 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) Metabolizer phenotype Genotype (Lower Score) Metabolizer 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

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 respectives alleles is heterozygous (0/1) in addition to heterozyous calls for the other variants that define the non-*1 allele in the genotype with the higher score.

Gene Genotype (Higher Score) Metabolizer phenotype Genotype (Lower Score) Metabolizer phenotype
CYP2C19 *1/*4 Intermediate *17/*4 Intermediate
CYP2C19 *1/*2 Intermediate *11/*2 Intermediate
CYP2C19 *1/*35 Intermediate *15/*35 Intermediate
CYP3A5 *1/*3 Intermediate *2/*3 Indeterminate
CYP3A5 *1/*3 Intermediate *4/*3 Indeterminate
CYP3A5 *1/*3 Intermediate *5/*3 Indeterminate
CYP3A5 *1/*3 Intermediate *9/*3 Indeterminate
CYP2B6 *1/*18 Intermediate *4/*18 Indeterminate

B. CPIC Allele Function, Phenotype and Recommendation

  1. All content is sourced from the CPIC database.

C. PharmCAT Exceptions to the CPIC Guideline Gene List

  1. PharmCAT does not determine CYP2D6, G6PD, MT-RNR1, or HLA genotypes from the vcf file, but genotypes for CYP2D6, G6PD, and MT-RNR1 can be provided to PharmCAT from an outside source and the corresponding phenotype and prescribing recommendations will be included in the generated report.
  2. HLAs are currently not included in PharmCAT.

D. 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 PharmCAT. 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 (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).

E. PharmGKB Disclaimers and Caveats

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