Providing information relevant to tamoxifen, codeine, and tramadol, as well as other medications metabolized by CYP2D6
Determining the exact genotype when other methods fail to generate this information or if genotype-phenotype discord is encountered clinically
Identifying exact genotyping when required (eg, drug trials, research protocols)
Identifying novel variants that may interfere with drug metabolism
Testing is done in 2 tiers when needed. Tier 1 uses a PCR-based 5'-nuclease assay to determine the variants present. All samples also have copy number determined by PCR-based 5'-nuclease assay. Testing in tier 1 allows for the detection of all common CYP2D6 variants (eg, *2, *3, *4, *5, *6, *7, *8, *9, *10, *17, *29, *35, *41) and rarer alleles such as *11, *12, *14A, *14B, and *15. Duplications and multiplications of alleles are also identified. Unitary and tandem CYP2D7-2D6 (*13) alleles and CYP2D6-2D7 (eg, *4N, *36, and *68) alleles can also be detected. Tier 2 testing involves sequencing using fluorescent dye-terminator chemistry and is only done if tier 1 testing results are ambiguous. Approximately 3% of samples require tier 2 testing.
Tier 2 testing will be performed only if an ambiguous phenotype is identified by tier 1 testing. The number of sequencing tests needed to determine the phenotype will vary depending on the tier 1 result.
See CYP2D6 Comprehensive Cascade Testing Algorithm in Special Instructions.
Tier 1: Real Time Polymerase Chain Reaction (PCR)
Tier 2: Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis
