Drug Response; Therapeutic management

Guidance for selecting a drug therapy and/or dose

Individuals needing preemptive or reactive genotyping for pharmacogenomic purposes.

Is research allowed on the sample after clinical testing is complete? Help
Research testing is only performed under IRB approved protocol with an opt-out policy in place.

Genomic DNA is extracted from whole blood. Genotyping for the CYP3A4 alleles is performed using a PCR-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to … Genomic DNA is extracted from whole blood. Genotyping for the CYP3A4 alleles is performed using a PCR-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected. Genotypes are assigned based on the allele-specific fluorescent signals that are detected.(User Guide: TaqMan SNP Genotyping Assay, Applied Biosystems Revision A.0 January 2014) View more

Other

Tests performed
Entire test performed in-house

Accuracy and analytical sensitivity for targeted simple variant(s) (SNVs and INDELs): (>99%).

Rare variants may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing could be considered. Samples may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples … Rare variants may be present that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing could be considered. Samples may contain donor DNA if obtained from patients who received non-leukoreduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing. CYP3A4 genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's CYP3A4 status. This test does not detect all variants that result in altered CYP3A4 activity. Therefore, absence of a detectable variant does not rule out the possibility that a patient has altered CYP3A4 metabolism due to other CYP3A4 variants that cannot be detected with this method. Furthermore, when 2 or more variants are identified, the cis-/trans- status (whether the variants are on the same or opposite chromosomes) is not always known. Drug-drug interactions and drug-metabolite inhibition must be considered. Drug-metabolite inhibition can occur, resulting in inhibition of CYP3A4 catalytic activity. Patients may also develop toxicity problems if liver and kidney function are impaired. CYP3A4 genotyping should not be ordered for managing patients receiving fluvastatin, rosuvastatin, or pravastatin since these drugs are not metabolized appreciably by CYP3A4. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP