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Test ID: 2D6CV Cytochrome P450 2D6 (CYP2D6) Comprehensive Cascade, Varies

Ordering Guidance

This test is not for use in assessing for autoimmune hepatitis. Autoantibodies for CYP2D6 enzyme are found in many cases of autoimmune hepatitis; order LKM / Liver/Kidney Microsome Type 1 Antibodies, Serum for autoimmune hepatitis assessment.


Testing is available as the single gene assay (this test) or as a part of a focused pharmacogenomics panel, which includes testing for the following genes: CYPs 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, 4F2, SLCO1B1, VKORC1. Order PGXFP / Focused Pharmacogenomics Panel if multiple pharmacogenomic genotype testing is desired.

Specimen Required

Multiple genotype tests can be performed on a single specimen after a single extraction. See Multiple Genotype Test List in Special Instructions for a list of tests that can be ordered together.


Submit only 1 of the following specimens:


Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred) 9 days/Refrigerated 30 days


Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 swab

Collection Instructions: Collect and send specimen per kit instructions.

Additional Information: Due to lower concentration of DNA yielded from saliva, testing cannot proceed to tier 2 sequencing and will stop after tier 1 testing is complete.

Specimen Stability Information: Ambient 30 days


Specimen Type: DNA

Container/Tube: 2 mL screw top tube

Specimen Volume: 100 mcL (microliters)

Collection Instructions:

1. The preferred volume is 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated


1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Cardiovascular Test Request (T724)

-Neurology Specialty Testing Client Test Request (T732)

-Therapeutics Test Request (T831)

Useful For

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 Algorithm

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.

Method Name

Tier 1: Real Time Polymerase Chain Reaction (PCR)

Tier 2: Polymerase Chain Reaction (PCR) followed by DNA Sequence Analysis

Reporting Name

CYP2D6 Genotype Cascade

Specimen Type


Specimen Minimum Volume

Blood: 1 mL
Saliva: 1 swab

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

The cytochrome P450 (CYP) family of enzymes is a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of the CYP enzymes, CYP2D6, is wholly or partially responsible for the metabolism of many commonly prescribed drugs.


The CYP2D6 gene is highly variable with over 100 named alleles. The gene may be deleted, duplicated, and multiplied, and can have multiple sequence variations. In addition, some individuals have genes that are hybrids of CYP2D6 and the CYP2D7 pseudogene. Some individuals have CYP2D6 variants that result in synthesis of an enzyme with decreased or absent catalytic activity. These individuals may process CYP2D6-metabolized medications more slowly. CYP2D6 duplications and multiplications involving active alleles may result in ultrarapid metabolism of CYP2D6-metabolized drugs. CYP2D6 genotype results are used to predict ultrarapid, rapid, normal (extensive), intermediate to normal (extensive), intermediate, poor to intermediate, and poor metabolizer phenotypes.(See Table 1)


Table 1. Enzyme Activity of Individual Star Alleles

Enzyme Activity

Examples of CYP2D6 star alleles

Normal (extensive) metabolism

*1, *35

Intermediate to normal activity


Decreased activity

*2, *9, *10, *14B, *17, *29, and *41

Negligible activity


No or null activity

*3, *4, *4N, *5, *6, *7, *8, *11, *12, *13, *14A, *15, *68


CYP2D6 phenotype is predicted based upon the number of functional, partially functional, and nonfunctional alleles present in a sample.


Phenotyping was derived from the Human Cytochrome P450 (CYP) Allele Nomenclature Committee website and the PharmGKB website for the related Clinical Pharmacogenetics Implementation Consortium guidelines.


There are instances where a phenotype prediction is not categorical and, in these instances, a range of possible phenotypes will be given. It should be noted that other laboratories may use different phenotype prediction methods as there is no consensus on this at this time. However, the method used here represents the findings of the majority of literature available at this time. Individuals without a detectable gene alteration will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP2D6 *1/*1.


Drugs that are metabolized through CYP2D6 may require dosage adjustment based on the individual patient's genotype. Patients who are poor metabolizers may require lower than usual doses to achieve optimal response in the case of drugs that are inactivated by the CYP2D6 enzyme and higher than usual doses in the case of drugs that are activated by CYP2D6 enzyme. Alternatively, patients who are ultrarapid metabolizers may benefit from increased doses in the case of drugs that are inactivated by CYP2D6 enzyme and lower doses in the case of drugs that are activated by CYP2D6. In the absence of clear guidance from FDA on dosing for various metabolizer phenotypes, patients with either ultrarapid or poor metabolism may benefit by switching to comparable alternate medications not primarily metabolized by CYP2D6 or by therapeutic drug monitoring where applicable.


Overall, this test provides a comprehensive CYP2D6 genotype result for patients, ensuring a more accurate phenotype prediction. This assay has clinical significance for patients taking or considering medications activated (eg, codeine, tramadol, and tamoxifen) or inactivated (eg, antidepressants and antipsychotics) by the CYP2D6 enzyme.


Sequential tier testing associated with this test will be initiated until the least ambiguous phenotype possible is determined.

Reference Values

A comprehensive interpretive report will be provided.


A comprehensive interpretive report will be provided that combines the results of all tier testing utilized to obtain the final genotype.


The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by the Pharmacogene Variation (PharmVar) Consortium.(1)


For the CYP2D6 Copy Number Variation assay, the reportable copy number range is 0 to 4 copies for each of the CYP2D6 region assessed.


Novel variants will be classified based on known, predicted, or possible effect on gene function and reported with interpretive comments detailing their potential or known significance.


For additional information regarding pharmacogenomic genes and their associated drugs, see Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Clinical Reference

1. Pharmacogene Variation Consortium database. Accessed 08/27/2018. Available at

2. Black JL, Walker DL, O'Kane DJ, Harmandayan M: Frequency of undetected CYP2D6 hybrid genes in clinical samples: impact on phenotype prediction. Drug Metab Dispos 2012;40(1):111-119

3. Goetz MP, Rae M, Suman VJ, et al: Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005;23:9312-9318

4. Kircheiner J, Nickchen K, Bauer M, et al: Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004;9:442-473

5. Crews KR, Gaedigk A, Dunnenberger HM, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2011 Feb;91(2):321-326

6. Hicks JK, Swen JJ, Thorn CF, et al: Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 2013 May:93(5):402-408

Day(s) Performed

Monday through Thursday

Report Available

3 to 16 days

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information


0071U-0076U (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2D6CV CYP2D6 Genotype Cascade 47403-1


Result ID Test Result Name Result LOINC Value
BA0113 CYP2D6 Genotype 40425-1
BA0114 CYP2D6 Phenotype 79715-9
BA0115 Interpretation 69047-9
BA0116 Additional Information 48767-8
BA0195 Method 49549-9
BA0196 Disclaimer 62364-5
BA0117 Reviewed by 18771-6

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
2D6S2 CYP2D6 GEN CYP2D6-2D7 HYBRID No, (Bill Only) No
2D6S3 CYP2D6 GEN CYP2D7-2D6 HYBRID No, (Bill Only) No
2D6S5 CYP2D6 5' GENE DUP/MLT No, (Bill Only) No
2D6S6 CYP2D6 3' GENE DUP/MLT No, (Bill Only) No
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: