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Test ID: 2D6Q Cytochrome P450 2D6 Comprehensive Cascade, Varies

Ordering Guidance

This test is not for use in assessing for autoimmune hepatitis. Autoantibodies for the 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) and as a part of a psychotropic or focused pharmacogenomics panel.


If multiple pharmacogenomic genotype testing is desired, order PGXQP / Focused Pharmacogenomics Panel, Varies.


If genotype testing for psychotropic medications is desired, order PSYQP / Psychotropic Pharmacogenomics Gene Panel, Varies.

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. Do not aliquot.

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: Extracted 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 cytochrome P450 2D6


Determining the exact genotype when other methods fail to generate this information or if genotype-phenotype discord is encountered clinically


Identifying precise genotype when required (eg, drug trials, research protocols)


Identifying novel variants that may interfere with drug metabolism (when reflex to sequencing is performed)

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, V

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 metabolizer phenotypes.(See Table 1)


Table 1. Enzyme Activity of Individual Star Alleles

Enzyme activity

Examples of CYP2D6 star alleles

Normal (extensive) metabolism

*1, *2, *2A, *35

Decreased activity

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

No or null activity

*3, *4, *4N, *5, *6, *7, *8, *11, *12, *13, *15, *36, *68, *114


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


Phenotyping is derived from the Pharmacogene Variation Consortium website (1), the Clinical Pharmacogenetics Implementation Consortium website (2), published guidelines (3-8), and an exhaustive review of the CYP2D6 literature (9-10).


There are instances where a precise phenotype prediction is not possible, and in these instances, a range of possible phenotypes will be given. 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, which 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. PharmVar: Pharmacogene Variation Consortium. Updated March 3, 2021. Accessed March 22, 2021. Available at

2. Clinical Pharmacogenetics Implementation Consortium (CPIC). Accessed October 14, 2020.

3. Brown JT, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Cytochrome P450 (CYP)2D6 Genotype and Atomoxetine Therapy. Clin Pharmacol Ther. 2019;106(1):94-102. doi: 10.1002/cpt.1409

4. Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95(4):376-382. doi: 10.1038/clpt.2013.254

5. Bell GC, Caudle KE, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron. Clin Pharmacol Ther. 2017;102(2):213-218. doi: 10.1002/cpt.598

6. Goetz MP, Sangkuhl K, Guchelaar HJ, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy. Clin Pharmacol Ther. 2018;103(5):770-777. doi: 10.1002/cpt.1007

7. Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Selective Serotonin Reuptake Inhibitors. Clin Pharmacol Ther. 2015;98(2):127-134. doi: 10.1002/cpt.147

8. Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017;102(1):37-44. doi: 10.1002/cpt.597

9. Black JL 3rd, Walker DL, O'Kane DJ, Harmandayan M. Frequency of undetected CYP2D6 hybrid genes in clinical samples: impact on phenotype prediction [published correction appears in Drug Metab Dispos. 2012 Jun;40(6):1238]. Drug Metab Dispos. 2012;40(1):111-119. doi: 10.1124/dmd.111.040832

10. Kirchheiner 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(5):442-473. doi: 10.1038/

11. Crews KR, Monte AA, Huddart R, et al: Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021 Jan 2. doi: 10.1002/cpt.2149. Epub ahead of print

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 US Food and Drug Administration.

CPT Code Information


0071U-0076U (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
2D6Q CYP2D6 Genotype Cascade, V 47403-1


Result ID Test Result Name Result LOINC Value
610103 CYP2D6 Genotype 40425-1
610104 CYP2D6 Phenotype 79715-9
610569 CYP2D6 Activity Score In Process
610105 Interpretation 69047-9
610106 Additional Information 48767-8
610107 Method 85069-3
610108 Disclaimer 62364-5
610109 Reviewed by 18771-6

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
2D61Z CYP2D6 Full Gene Sequence No, (Bill Only) No
2D62Z CYP2D6 GEN CYP2D6-2D7 Hybrid No, (Bill Only) No
2D63Z CYP2D6 GEN CYP2D7-2D6 Hybrid No, (Bill Only) No
2D64Z CYP2D6 Nonduplicated Gene No, (Bill Only) No
2D65Z CYP2D6 5' Gene DUP/MLT No, (Bill Only) No
2D66Z CYP2D6 3' Gene DUP/MLT No, (Bill Only) No
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information: