Summary & Overview
CPT 81291: MTHFR Gene Common Variant Detection
CPT code 81291 represents a molecular laboratory test that detects common variants in the MTHFR gene. This technical laboratory procedure is clinically relevant for evaluations where MTHFR variants may inform metabolic, thrombotic, or pharmacogenomic considerations. The code matters nationally because genetic testing utilization and coverage policies affect access to diagnostic information used in diverse clinical settings, from outpatient clinics to hospital laboratories.
Key payers discussed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the clinical purpose of the test, typical sites where the technical component is performed, and what to expect in payer coverage discussions. The publication outlines benchmarks and policy-related considerations, clinical context for when MTHFR variant testing is ordered, and practical coding and billing elements tied to the technical laboratory service. Data not available in the input for specific reimbursement benchmarks, associated taxonomies, and ICD-10 diagnoses is noted where applicable.
Billing Code Overview
CPT code 81291 describes a laboratory test in which a lab analyst performs the technical component to detect common variants in the gene for 5,10–methylenetetrahydrofolate reductase (MTHFR). This service is a molecular diagnostic genetic test focused on identifying common genetic changes in MTHFR that can be relevant to metabolic and thrombotic evaluations.
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Service type: Molecular diagnostic genetic testing (technical component)
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Typical site of service: Clinical laboratory or hospital laboratory setting where molecular testing is performed.
Data not available in the input for payers, associated taxonomies, ICD-10 diagnoses, related codes, and service line.
Clinical & Coding Specifications
Clinical Context
A typical patient is an adult or adolescent referred by a primary care physician, genetic counselor, or obstetrician for targeted genotyping of common methylenetetrahydrofolate reductase (MTHFR) gene variants. Common clinical indications include evaluation of unexplained recurrent pregnancy loss, suspected hyperhomocysteinemia, family history of MTHFR variants, or as part of thrombophilia workup in a patient with venous thromboembolism. The workflow begins with outpatient order entry specifying 81291, collection of a peripheral blood sample or buccal swab at an ambulatory clinic or specialty practice, specimen labeling and shipment to a molecular diagnostics laboratory. The laboratory performs the technical assay to detect common MTHFR sequence changes (for example, C677T and A1298C) and generates a report of detected variants. The report is reviewed by a laboratory director or pathologist, the professional interpretation (if billed separately) is provided to the ordering clinician, and results are incorporated into the patient’s electronic health record for follow-up counseling or management by the ordering provider.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | Use when billing only the professional interpretation component if the laboratory separates technical and professional components. |