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CPT 81226: CYP2D6 Genetic Variant Detection

CPT code 81226 represents molecular laboratory testing to detect common genetic changes in the CYP2D6 gene, a key enzyme in drug metabolism. Nationally, CYP2D6 testing informs pharmacogenomic-guided prescribing across multiple therapeutic areas, making this code relevant for precision medicine programs and outpatient laboratory services. The code covers the technical laboratory component of detecting CYP2D6 variants.

Key payers addressed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find an overview of clinical context for CYP2D6 testing, the typical service setting, and payer relevance. The publication summarizes benchmark considerations for coverage and utilization, highlights policy and coding updates affecting laboratory reporting, and outlines implications for laboratory and clinical workflows. Practical information includes service line placement and typical sites of service for this technical molecular assay.

Data not available in the input for associated taxonomies, ICD-10 diagnoses, and related codes. The content is intended to inform coding, billing, and policy stakeholders about the clinical purpose and payer landscape for CPT code 81226 at a national level.

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Billing Code Overview

CPT code 81226 describes a laboratory test performed by a lab analyst to detect common genetic variants in the CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6). This test identifies alterations that can affect drug metabolism, supporting medication selection and dosing decisions in clinical care.

Service type: Clinical diagnostic molecular laboratory testing
Typical site of service: Clinical diagnostic laboratory or outpatient laboratory facility

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CPT 81226: CYP2D6 Genetic Variant Detection

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Billing Code Overview

Service type: Clinical diagnostic molecular laboratory testing
Typical site of service: Clinical diagnostic laboratory or outpatient laboratory facility

Clinical & Coding Specifications

Clinical Context

A 45-year-old patient with a history of chronic depression and prior inadequate response to selective serotonin reuptake inhibitors (SSRIs) is referred for pharmacogenetic testing to guide medication selection. The ordering clinician—commonly a psychiatrist, primary care physician, or clinical pharmacologist—requests genotyping of the cytochrome P450 2D6 gene to detect common variant alleles that affect drug metabolism. A phlebotomy or buccal swab specimen is collected in an outpatient clinic or ambulatory laboratory; the specimen is sent to a molecular diagnostics laboratory where a clinical laboratory scientist performs 81226 testing using validated genotyping methods. Results are reported back to the ordering provider and incorporated into medication management decisions, typically alongside clinical interpretation reporting metabolizer status (e.g., poor, intermediate, normal, ultrarapid). Typical sites of service include independent clinical diagnostic laboratories, hospital-based molecular pathology labs, and outpatient ambulatory care centers that collect specimens for send-out testing. The workflow includes order entry, specimen collection and accessioning, DNA extraction, targeted genotyping for common CYP2D6 variants, analytical verification, and result reporting with phenotype interpretation for medications metabolized by CYP2D6 such as certain antidepressants, antipsychotics, beta-blockers, and opioids.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional (interpretation) portion of the test when separate technical component billed by the lab (`TC`).
`TC`	Technical component	Use when billing only the technical component (laboratory processing, instrumentation).
`90`	Reference (outside) laboratory	Use when the specimen is sent to an outside laboratory for testing and billing reflects reference lab processing.
`59`	Distinct procedural service	Use sparingly to indicate a distinct service when another unrelated procedure occurs on same day and distinct by CPT definitions.
`52`	Reduced services	Use when the service is partially reduced or not fully performed.
`53`	Discontinued procedure	Use if testing was started but discontinued for clinical reasons before completion.
`22`	Increased procedural services	Use when documentation supports substantially greater work or complexity for the test beyond typical processing.
`90`	Reference (outside) laboratory	Use when an independent outside laboratory performs the testing and bills separately.
`QK`	Medical direction of two or more qualified individuals (molecular pathology context)	Use when applicable under molecular pathology supervision rules for directed staff.
`QX`	Attending practitioner’s certification of assistant presence (when applicable)	Use in limited scenarios where auxiliary personnel involvement is separately reportable.
`59`	Distinct procedural service	Use to indicate services not normally reported together when clinically separate.

Taxonomy Code	Specialty	Notes
207RG0100X	Clinical Pathology	Pathologists and laboratory medicine physicians overseeing molecular testing and result interpretation.
208000000X	Medical Genetics	Clinical geneticists or genetic counselors ordering and interpreting pharmacogenetic tests.
207Q00000X	Clinical Molecular Genetics Laboratory	Laboratory directors and clinical laboratorians who perform and supervise `CYP2D6` genotyping.
2084P0800X	Psychiatry	Psychiatrists who commonly order pharmacogenetic testing to inform psychotropic medication selection.
207P00000X	Pathology & Laboratory Medicine	Clinical laboratory specialists responsible for technical processing and quality control.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`F32.9`	Major depressive disorder, single episode, unspecified	Depression is a common indication for CYP2D6 testing when patients have poor response or adverse effects to antidepressants metabolized by CYP2D6.
`F33.1`	Major depressive disorder, recurrent, moderate	Recurrent depression may prompt pharmacogenetic testing to optimize long-term medication management.
`Z13.79`	Encounter for screening for other conditions	Used for preventive or screening pharmacogenetic testing when ordered as part of medication optimization.
`G89.3`	Neoplasm related pain (chronic pain)	CYP2D6 testing can guide opioid selection/metabolism for chronic pain management.
`I10`	Essential (primary) hypertension	Certain beta-blockers metabolized by CYP2D6 may require dosing or drug selection informed by genotype.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81225`	CYP2C19 (cyclooxygenase P450 2C19) gene sequencing or genotyping assay	Often ordered alongside `81226` when broader pharmacogenetic panels are requested for antidepressant or antiplatelet therapy guidance.
`81479`	Unlisted molecular pathology procedure	Used for reporting atypical or custom pharmacogenetic tests not covered by specific CPT codes; occasionally used if test methods extend beyond standard panels.
`0036U`	Pharmacogenomic gene panel, multiple genes (registry/PLA may vary)	Commercial pharmacogenomic panel codes or proprietary PLA codes may be billed when `CYP2D6` is part of a multi-gene panel; they are used in bundled or panel testing workflows.
`99000`	Handling and/or conveyance of specimen (when applicable)	Ancillary facility or courier charges may be billed separately by some entities for specimen transport in send-out testing workflows.
`83036`	Hemoglobin A1c (example of unrelated lab test)	Represents other laboratory monitoring tests that may be performed in the same visit but are independent of `81226` testing; use of distinct modifiers may apply if billed same day.

CPT 81105: HPA-1 (CD61/ITGB3) Platelet Antigen Genotyping

CPT-81106-HPA-2-T145M-GENETIC-ALLELE-ANALYSIS

CPT 81106: HPA-2 (T145M) Genetic Allele Analysis

CPT-81107-HPA-3-GENETIC-ANALYSIS-TECHNICAL-COMPONENT

CPT 81107: HPA‑3 (I843S) Platelet Antigen Genotyping

CPT-81108-HPA-4-R143Q-GENOTYPING

CPT 81108: HPA-4 (R143Q) Genotyping, Technical Component

CPT-81109-HPA-5-K505E-GENETIC-ANALYSIS

CPT 81109: HPA-5 (K505E) Genetic Analysis

CPT-81110-HPA-6-R489Q-GENOTYPING

CPT 81110: HPA-6 (R489Q) Genotyping, Technical Component

CPT-81111-HPA-9-V837M-ALLELE-ANALYSIS

CPT 81111: HPA-9 (V837M) Allele Analysis, Laboratory Technical Component

CPT-81112-HPA-15-GENETIC-ANALYSIS-S682Y

CPT 81112: HPA-15 (S682Y) Genetic Analysis

CPT-81120-IDH1-MOLECULAR-DIAGNOSTIC-TEST

CPT 81120: IDH1 Molecular Diagnostic Test

CPT-81121-IDH2-MOLECULAR-DIAGNOSTIC-TEST

CPT 81121: IDH2 (NADP+) Molecular Diagnostic Test

Showing 1–10 of 199

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

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Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional (interpretation) portion of the test when separate technical component billed by the lab (`TC`).
`TC`	Technical component	Use when billing only the technical component (laboratory processing, instrumentation).
`90`	Reference (outside) laboratory	Use when the specimen is sent to an outside laboratory for testing and billing reflects reference lab processing.
`59`	Distinct procedural service	Use sparingly to indicate a distinct service when another unrelated procedure occurs on same day and distinct by CPT definitions.
`52`	Reduced services	Use when the service is partially reduced or not fully performed.
`53`	Discontinued procedure	Use if testing was started but discontinued for clinical reasons before completion.
`22`	Increased procedural services	Use when documentation supports substantially greater work or complexity for the test beyond typical processing.
`90`	Reference (outside) laboratory	Use when an independent outside laboratory performs the testing and bills separately.
`QK`	Medical direction of two or more qualified individuals (molecular pathology context)	Use when applicable under molecular pathology supervision rules for directed staff.
`QX`	Attending practitioner’s certification of assistant presence (when applicable)	Use in limited scenarios where auxiliary personnel involvement is separately reportable.
`59`	Distinct procedural service	Use to indicate services not normally reported together when clinically separate.

Taxonomy Code	Specialty	Notes
207RG0100X	Clinical Pathology	Pathologists and laboratory medicine physicians overseeing molecular testing and result interpretation.
208000000X	Medical Genetics	Clinical geneticists or genetic counselors ordering and interpreting pharmacogenetic tests.
207Q00000X	Clinical Molecular Genetics Laboratory	Laboratory directors and clinical laboratorians who perform and supervise `CYP2D6` genotyping.
2084P0800X	Psychiatry	Psychiatrists who commonly order pharmacogenetic testing to inform psychotropic medication selection.
207P00000X	Pathology & Laboratory Medicine	Clinical laboratory specialists responsible for technical processing and quality control.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`F32.9`	Major depressive disorder, single episode, unspecified	Depression is a common indication for CYP2D6 testing when patients have poor response or adverse effects to antidepressants metabolized by CYP2D6.
`F33.1`	Major depressive disorder, recurrent, moderate	Recurrent depression may prompt pharmacogenetic testing to optimize long-term medication management.
`Z13.79`	Encounter for screening for other conditions	Used for preventive or screening pharmacogenetic testing when ordered as part of medication optimization.
`G89.3`	Neoplasm related pain (chronic pain)	CYP2D6 testing can guide opioid selection/metabolism for chronic pain management.
`I10`	Essential (primary) hypertension	Certain beta-blockers metabolized by CYP2D6 may require dosing or drug selection informed by genotype.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81225`	CYP2C19 (cyclooxygenase P450 2C19) gene sequencing or genotyping assay	Often ordered alongside `81226` when broader pharmacogenetic panels are requested for antidepressant or antiplatelet therapy guidance.
`81479`	Unlisted molecular pathology procedure	Used for reporting atypical or custom pharmacogenetic tests not covered by specific CPT codes; occasionally used if test methods extend beyond standard panels.
`0036U`	Pharmacogenomic gene panel, multiple genes (registry/PLA may vary)	Commercial pharmacogenomic panel codes or proprietary PLA codes may be billed when `CYP2D6` is part of a multi-gene panel; they are used in bundled or panel testing workflows.
`99000`	Handling and/or conveyance of specimen (when applicable)	Ancillary facility or courier charges may be billed separately by some entities for specimen transport in send-out testing workflows.
`83036`	Hemoglobin A1c (example of unrelated lab test)	Represents other laboratory monitoring tests that may be performed in the same visit but are independent of `81226` testing; use of distinct modifiers may apply if billed same day.

CPT 81105: HPA-1 (CD61/ITGB3) Platelet Antigen Genotyping

CPT-81106-HPA-2-T145M-GENETIC-ALLELE-ANALYSIS

CPT 81106: HPA-2 (T145M) Genetic Allele Analysis

CPT-81107-HPA-3-GENETIC-ANALYSIS-TECHNICAL-COMPONENT

CPT 81107: HPA‑3 (I843S) Platelet Antigen Genotyping

CPT-81108-HPA-4-R143Q-GENOTYPING

CPT 81108: HPA-4 (R143Q) Genotyping, Technical Component

CPT-81109-HPA-5-K505E-GENETIC-ANALYSIS

CPT 81109: HPA-5 (K505E) Genetic Analysis

CPT-81110-HPA-6-R489Q-GENOTYPING

CPT 81110: HPA-6 (R489Q) Genotyping, Technical Component

CPT-81111-HPA-9-V837M-ALLELE-ANALYSIS

CPT 81111: HPA-9 (V837M) Allele Analysis, Laboratory Technical Component

CPT-81112-HPA-15-GENETIC-ANALYSIS-S682Y

CPT 81112: HPA-15 (S682Y) Genetic Analysis

CPT-81120-IDH1-MOLECULAR-DIAGNOSTIC-TEST

CPT 81120: IDH1 Molecular Diagnostic Test

CPT-81121-IDH2-MOLECULAR-DIAGNOSTIC-TEST

CPT 81121: IDH2 (NADP+) Molecular Diagnostic Test

Showing 1–10 of 199

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

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CPT 81226: CYP2D6 Genetic Variant Detection

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Billing Code Overview

OpenPayer

CPT 81226: CYP2D6 Genetic Variant Detection

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Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

CPT 81226: CYP2D6 Genetic Variant Detection

Sign up for cpt 81226 policy alerts

Billing Code Overview

CPT 81226: CYP2D6 Genetic Variant Detection

Sign up for cpt 81226 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81226 represent and where is it typically performed?

Which billing modifiers apply to 81226 and when should they be used?

Who typically orders CYP2D6 testing under 81226 and for what clinical reasons?

How does 81226 relate to other CPT or panel codes in pharmacogenetic testing?

What ICD-10 diagnoses are commonly associated with billing CPT 81226?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81226 represent and where is it typically performed?

Which billing modifiers apply to 81226 and when should they be used?

Who typically orders CYP2D6 testing under 81226 and for what clinical reasons?

How does 81226 relate to other CPT or panel codes in pharmacogenetic testing?

What ICD-10 diagnoses are commonly associated with billing CPT 81226?

References