Title | pharmcat_positions |
---|---|
Date created | May 05, 2022 |
PharmCAT Version | v1.7.0-6-gfc523f3a |
CPIC Version | v.1.17.1 |
Genotypes called: 20 / 21
Drugs | Gene | Genotype | Allele Functionality | Phenotype | Missing Variant Input* |
---|---|---|---|---|---|
ABCG2 |
rs2231142 reference (G)/rs2231142 reference (G)
|
Two normal function alleles
|
Normal Function
|
No | |
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 | |
HLA-B |
*15:02/*57:01
|
N/A
|
*15:02 positive; *57:01 positive; *58:01 negative
|
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 |
Type | Annotation |
---|---|
Population | general |
Implication for HLA-B | Significantly increased risk of abacavir hypersensitivity |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-B | HLA-B*57:01 positive |
Recommendation | Abacavir is not recommended |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for HLA-B | Low or reduced risk of allopurinol-induced SCAR |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-B | HLA-B*58:01 negative |
Recommendation | Use allopurinol per standard dosing guidelines |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 CYP2C19 | Normal metabolism of tertiary amines |
Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Phenotype for CYP2C19 | Normal Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
Classification of Recommendation | Moderate |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | general |
Implication for UGT1A1 | Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir. |
Matched Diplotypes | UGT1A1:*1/*1 |
Phenotype for UGT1A1 | Normal Metabolizer |
Recommendation | There 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 Recommendation | Strong |
Comments | All 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:
Type | Annotation |
---|---|
Population | pediatrics |
Implication for CYP2D6 | Possibly 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 Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Initiate 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 Recommendation | Moderate |
Comments | Therapeutic 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. |
Type | Annotation |
---|---|
Population | adults |
Implication for CYP2D6 | Possibly 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 Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Initiate 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 Recommendation | Moderate |
Comments | Therapeutic 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:
Type | Annotation |
---|---|
Population | population general |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | SLCO1B1:*1/*1 |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for TPMT | Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression. |
Implication for NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
Phenotype for TPMT | Normal Metabolizer |
Phenotype for NUDT15 | Normal Metabolizer |
Recommendation | Start 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 Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for DPYD | Normal DPD activity and "normal" risk for fluoropyrimidine toxicity |
Matched Diplotypes | DPYD:Reference/Reference |
Phenotype for DPYD | Normal Metabolizer |
Activity Score for DPYD | 2.0 |
Recommendation | Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | CBZ use >3mos |
Implication for HLA-A | n/a |
Implication for HLA-B | Greater risk of carbamazepine-induced SJS/TEN |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-A | No HLA-A Result |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used carbamazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of carbamazepine in the future. |
Classification of Recommendation | Optional |
Comments | Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered. |
Type | Annotation |
---|---|
Population | CBZ naive |
Implication for HLA-A | n/a |
Implication for HLA-B | Greater risk of carbamazepine-induced SJS/TEN |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-A | No HLA-A Result |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If patient is carbamazepine-naïve, do not use carbamazepine. |
Classification of Recommendation | Strong |
Comments | Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered. |
Type | Annotation |
---|---|
Population | CBZ-no alternatives |
Implication for HLA-A | n/a |
Implication for HLA-B | Greater risk of carbamazepine-induced SJS/TEN |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-A | No HLA-A Result |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If patient is carbamazepine-naïve, do not use carbamazepine. |
Classification of Recommendation | Strong |
Comments | Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Previous tolerance of carbamazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. In addition to HLA-B*15:02, risk for carbamazepine-induced SJS/TEN has been reported in association with the most common B75 serotype alleles in Southeast Asia, HLA-B*15:08, HLA-B*15:11, and HLA-B*15:21. Although not described, the possibility of carbamazepine-induced SJS/TEN in association with less frequently carried B75 serotype alleles, such as HLA-B*15:30 and HLA-B*15:31, should also be considered. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal metabolism |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate therapy with recommended starting dose |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 CYP2C19 | Normal metabolism of tertiary amines |
Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Phenotype for CYP2C19 | Normal Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
Classification of Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | CVI ACS PCI |
Implication for CYP2C19 | Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | If considering clopidogrel, use at standard dose (75 mg/day) |
Classification of Recommendation | Strong |
Comments | 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. |
Type | Annotation |
---|---|
Population | NVI |
Implication for CYP2C19 | Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | If considering clopidogrel, use at standard dose (75 mg/day) |
Classification of Recommendation | Strong |
Comments | 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. |
Type | Annotation |
---|---|
Population | CVI non-ACS non-PCI |
Implication for CYP2C19 | Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | If considering clopidogrel, use at standard dose (75 mg/day) |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced morphine formation |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1 |
Recommendation | Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid. |
Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider 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 Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate 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 Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 CYP2C19 | Normal metabolism of tertiary amines |
Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Phenotype for CYP2C19 | Normal Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
Classification of Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | child >40kg_adult |
Implication for CYP2B6 | Normal efavirenz metabolism |
Matched Diplotypes | CYP2B6:*1/*1 |
Phenotype for CYP2B6 | Normal Metabolizer |
Recommendation | Initiate efavirenz with standard dosing (600 mg/day) |
Classification of Recommendation | Strong |
Comments | 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). |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal metabolism |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate therapy with recommended starting dose |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for DPYD | Normal DPD activity and "normal" risk for fluoropyrimidine toxicity |
Matched Diplotypes | DPYD:Reference/Reference |
Phenotype for DPYD | Normal Metabolizer |
Activity Score for DPYD | 2.0 |
Recommendation | Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal exposure. |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure. |
Matched Diplotypes | CYP2C9:*1/*1, SLCO1B1:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Phenotype for SLCO1B1 | Normal Function |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Initiate therapy with recommended starting dose. |
Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | PHT naive |
Implication for HLA-B | Increased risk of phenytoin-induced SJS/TEN |
Implication for CYP2C9 | Normal phenytoin metabolism |
Matched Diplotypes | CYP2C9:*1/*1, HLA-B:*15:02/*57:01 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine. |
Classification of Recommendation | Strong |
Comments | Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. |
Type | Annotation |
---|---|
Population | PHT use >3mos |
Implication for HLA-B | Increased risk of phenytoin-induced SJS/TEN |
Implication for CYP2C9 | Normal phenytoin metabolism |
Matched Diplotypes | CYP2C9:*1/*1, HLA-B:*15:02/*57:01 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing. |
Classification of Recommendation | Optional |
Comments | Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Minimal evidence for pharmacokinetic or clinical effect. |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1 |
Recommendation | Use 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 Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 CYP2C19 | Normal metabolism of tertiary amines |
Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Phenotype for CYP2C19 | Normal Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
Classification of Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CFTR | An 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 Diplotypes | CFTR:No CPIC variants found |
Phenotype for CFTR | ivacaftor non-responsive in CF patients |
Recommendation | Ivacaftor is not recommended |
Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate 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 Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | population general |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | SLCO1B1:*1/*1 |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for TPMT | Lower concentrations of TGN metabolites, higher MeTIMP, this is the ‘normal’ pattern. Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression. |
Implication for NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
Phenotype for TPMT | Normal Metabolizer |
Phenotype for NUDT15 | Normal Metabolizer |
Recommendation | Start 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 Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider 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 Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate 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 Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Very limited data available for CYP2D6 intermediate metabolizers |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. |
Classification of Recommendation | No Recommendation |
Comments | Drug-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:
Type | Annotation |
---|---|
Population | OXC naive |
Implication for HLA-B | Greater risk of oxcarbazepine-induced SJS/TEN |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If patient is oxcarbazepine-naïve, do not use oxcarbazepine. |
Classification of Recommendation | Strong |
Comments | Other aromatic anticonvulsants have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. |
Type | Annotation |
---|---|
Population | OXC use >3 mos |
Implication for HLA-B | Greater risk of oxcarbazepine-induced SJS/TEN |
Matched Diplotypes | HLA-B:*15:02/*57:01 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (~4-28 days), and cases usually occur within three months of dosing; therefore, if the patient has previously used oxcarbazepine consistently for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of oxcarbazepine in the future. |
Classification of Recommendation | Optional |
Comments | Previous tolerance of oxcarbazepine is not indicative of tolerance to other aromatic anticonvulsants. Aromatic anticonvulsants include carbamazepine, oxcarbazepine, eslicarbazepine, lamotrigine, phenytoin, fosphenytoin, and phenobarbital. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal PPI metabolism; may be at increased risk of therapeutic failure compared to CYP2C19 IMs and PMs |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate 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 Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced metabolism when compared to normal metabolizers. Higher plasma concentrations may increase the probability of side effects. |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Initiate therapy with recommended starting dose |
Classification of Recommendation | Moderate |
For more information read the guideline on cpicpgx.org.
Citations:
For more information read the guideline on cpicpgx.org.
Citations:
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | PHT use >3mos |
Implication for HLA-B | Increased risk of phenytoin-induced SJS/TEN |
Implication for CYP2C9 | Normal phenytoin metabolism |
Matched Diplotypes | CYP2C9:*1/*1, HLA-B:*15:02/*57:01 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If the patient has previously used phenytoin continuously for longer than three months without incidence of cutaneous adverse reactions, cautiously consider use of phenytoin in the future. The latency period for drug-induced SJS/TEN is short with continuous dosing and adherence to therapy (4-28 days), and cases usually occur within three months of dosing. |
Classification of Recommendation | Optional |
Comments | Previous tolerance of phenytoin is not indicative of tolerance to other aromatic anticonvulsants. |
Type | Annotation |
---|---|
Population | PHT naive |
Implication for HLA-B | Increased risk of phenytoin-induced SJS/TEN |
Implication for CYP2C9 | Normal phenytoin metabolism |
Matched Diplotypes | CYP2C9:*1/*1, HLA-B:*15:02/*57:01 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Allele Status for HLA-B | HLA-B*15:02 positive |
Recommendation | If patient is phenytoin-naive, do not use phenytoin/fosphenytoin. Avoid carbamazepine and oxcarbazepine. |
Classification of Recommendation | Strong |
Comments | Other aromatic anticonvulsants, including eslicarbazepine, lamotrigine, and phenobarbital, have weaker evidence linking SJS/TEN with the HLA-B*15:02 allele; however, caution should still be used in choosing an alternative agent. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | population general |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | SLCO1B1:*1/*1 |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | population general |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | SLCO1B1:*1/*1 |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for G6PD | Low or reduced risk of hemolytic anemia |
Matched Diplotypes | G6PD:B (wildtype)/B (wildtype) |
Phenotype for G6PD | Normal |
Recommendation | No reason to withhold rasburicase based on G6PD status. |
Classification of Recommendation | Strong |
Comments | A 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:
Type | Annotation |
---|---|
Population | general |
Implication for ABCG2 | Typical myopathy risk and rosuvastatin exposure |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | ABCG2:rs2231142 reference (G)/rs2231142 reference (G), SLCO1B1:*1/*1 |
Phenotype for ABCG2 | Normal Function |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and specific population guidelines. |
Classification of Recommendation | Strong |
Comments | The potential for drug-drug interactions and dose limits based on renal and hepatic function and Asian ancestry should be evaluated prior to initiating rosuvastatin. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C19 | Normal metabolism |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate therapy with recommended starting dose |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for SLCO1B1 | Typical myopathy risk and statin exposure |
Matched Diplotypes | SLCO1B1:*1/*1 |
Phenotype for SLCO1B1 | Normal Function |
Recommendation | Prescribe desired starting dose and adjust doses based on disease-specific guidelines. |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for RYR1 | These 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 CACNA1S | These 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 Diplotypes | CACNA1S:Reference/Reference, RYR1:Reference/Reference |
Phenotype for RYR1 | Uncertain Susceptibility |
Phenotype for CACNA1S | Uncertain Susceptibility |
Recommendation | Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants. |
Classification of Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP3A5 | Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations. |
Matched Diplotypes | CYP3A5:*1/*1 |
Phenotype for CYP3A5 | Normal Metabolizer |
Recommendation | Increase 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 Recommendation | Strong |
Comments | This 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers. |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider 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 Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2C9 | Normal metabolism |
Matched Diplotypes | CYP2C9:*1/*1 |
Phenotype for CYP2C9 | Normal Metabolizer |
Activity Score for CYP2C9 | 2.0 |
Recommendation | Initiate 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 Recommendation | Strong |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for TPMT | Lower 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 NUDT15 | Normal risk of thiopurine-related leukopenia, neutropenia, myelosuppression |
Matched Diplotypes | NUDT15:*1/*1, TPMT:*1/*1 |
Phenotype for TPMT | Normal Metabolizer |
Phenotype for NUDT15 | Normal Metabolizer |
Recommendation | Start 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 Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for MT-RNR1 | Very high risk of developing hearing loss if administered an aminoglycoside antibiotic. |
Matched Diplotypes | MT-RNR1:1555A>G |
Phenotype for MT-RNR1 | increased risk of aminoglycoside-induced hearing loss |
Recommendation | Avoid 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 Recommendation | Strong |
Comments | If 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced O-desmethyltramadol (active metabolite) formation |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1 |
Recommendation | Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid. |
Classification of Recommendation | Optional |
For more information read the guideline on cpicpgx.org.
Citations:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Reduced 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 CYP2C19 | Normal metabolism of tertiary amines |
Matched Diplotypes | CYP2C19:*38/*38, CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Phenotype for CYP2C19 | Normal Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Consider a 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. |
Classification of Recommendation | Optional |
Comments | 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. 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:
Type | Annotation |
---|---|
Population | general |
Implication for CYP2D6 | Very limited data available for CYP2D6 intermediate metabolizers |
Matched Diplotypes | CYP2D6:*1/*3 |
Phenotype for CYP2D6 | Intermediate Metabolizer |
Activity Score for CYP2D6 | 1.0 |
Recommendation | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. |
Classification of Recommendation | No Recommendation |
Comments | Drug-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:
Type | Annotation |
---|---|
Population | adults |
Implication for CYP2C19 | Normal voriconazole metabolism |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate therapy with recommended standard of care dosing |
Classification of Recommendation | Strong |
Comments | 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. |
Type | Annotation |
---|---|
Population | pediatrics |
Implication for CYP2C19 | Normal voriconazole metabolism |
Matched Diplotypes | CYP2C19:*38/*38 |
Phenotype for CYP2C19 | Normal Metabolizer |
Recommendation | Initiate therapy with recommended standard of care dosing |
Classification of Recommendation | Strong |
Comments | 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. |
For more information read the guideline on cpicpgx.org.
Citations:
For more information read the guideline on cpicpgx.org.
Citations:
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr4:88131171 | rs2231142 | G|G | G | rs2231142 variant (T) |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr1:201060815 | rs1800559 | C|C | C | c.3257G>A |
|
chr1:201091993 | rs772226819 | G|G | G | c.520C>T |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr10:94938683 | rs114071557 | A|A | A | *36 |
|
chr10:94938719 | T|T | T | *80 |
|
|
chr10:94938737 | rs67807361 | C|C | C | *7 |
|
chr10:94938771 | rs142240658 | C|C | C | *21 |
|
chr10:94938788 | C|C | C | *83 |
|
|
chr10:94938800 | rs1364419386 | G|G | G | *76 |
|
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 |
|
chr10:94941975 | G|G | G | *77 |
|
|
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 |
|
chr10:94942243 | rs1375956433 | T|T | T | *78 |
|
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 |
|
chr10:94942306 | rs1289704600 | C|C | C | *72 |
|
chr10:94942308 | rs17847037 | C|C | C | *73 |
|
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 |
|
chr10:94947939 | rs370100007 | G|G | G | *74 |
|
chr10:94949129 | A|A | A | *49 |
|
|
chr10:94949144 | C|C | C | *50 |
|
|
chr10:94949145 | rs772782449 | C|C | C | *82 |
|
chr10:94949161 | AT|AT | AT | *85 |
|
|
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 |
|
chr10:94972183 | A|A | A | *81 |
|
|
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 |
|
chr10:94981258 | rs1297714792 | C|C | C | *79 |
|
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 |
|
chr10:94986136 | rs1254213342 | A|A | A | *75 |
|
chr10:94986174 | rs1441296358 | G|G | G | *84 |
|
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 |
|
Position in VCF | RSID | Call in VCF |
---|---|---|
chr10:94645745 | rs12777823 | G|G |
Phasing status: Unavailable for calls made outside PharmCAT
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr7:99652770 | rs41303343 | T|T | T | *7 |
|
chr7:99660516 | rs28383479 | C|C | C | *9 |
|
chr7:99665212 | rs10264272 | C|C | C | *6 |
|
chr7:99672916 | rs776746 | T|T | T | *3 |
|
chr7:99676198 | rs55817950 | G|G | G | *8 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr19:15879621 | rs2108622 | C|C | C | *3 |
|
chr19:15897578 | rs3093105 | A|A | A | *2 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Unavailable for calls made outside PharmCAT
Phasing status: Unphased
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.
Phasing status: Unavailable for calls made outside PharmCAT
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr19:39248147 | rs12979860 | C|C | C | rs12979860 variant (T) |
|
Phasing status: Unavailable for calls made outside PharmCAT
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
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 |
|
Phasing status: Phased
Position in VCF | RSID | Call in VCF | Reference | Related Alleles | Warnings |
---|---|---|---|---|---|
chr16:31096368 | rs9923231 | C|C | C | rs9923231 variant (T) |
|
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.
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.
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.
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.
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.
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.
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 |
SLCO1B1 | *1/*46 | Decreased function | *15/*45 | Indeterminate |
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 | Indeterminate |
SLCO1B1 | *1/*32 | Indeterminate | *4/*24 | Indeterminate |
SLCO1B1 | *1/*40 | Indeterminate | *5/*19 | Indeterminate |
SLCO1B1 | *1/*43 | Indeterminate | *4/*44 | Indeterminate |
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 |