Summary & Overview
CPT 81357: U2AF1 Mutation Analysis for Hematologic Disorders
CPT code 81357 denotes a molecular diagnostic assay for detecting prevalent sequence changes in the U2AF1 gene, including S34 and Q157 variants. This testing is clinically relevant for patients with suspected or confirmed hematologic malignancies, where mutation status can influence diagnostic classification and prognosis. Nationally, molecular profiling for myeloid and other blood disorders has grown in clinical importance as targeted therapies and risk stratification rely on genetic findings.
Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of service definition, typical sites of care, and the clinical context for ordering the test. The publication also summarizes payer coverage patterns and benchmarks where available, highlights policy and coding considerations affecting laboratory billing, and situates CPT code 81357 within broader molecular diagnostic service lines. Clinical implications for hematologic diagnosis and prognostication are outlined to clarify why the code is used and how results may inform care. Data not available in the input are noted explicitly where applicable.
Billing Code Overview
CPT code 81357 describes a laboratory molecular test performed on a specimen (for example, blood) to detect common sequence changes in the U2AF1 (U2 small nuclear RNA auxiliary factor 1) gene, including variants such as S34F, S34Y, Q157R, and Q157P. The test identifies somatic mutations that can inform diagnosis and prognosis of hematologic disorders, particularly various leukemias.
Service type: Molecular diagnostic laboratory test (genetic sequencing or targeted mutation analysis)
Typical site of service: Clinical laboratory or hospital laboratory processing patient specimens (blood or other appropriate biological samples)
Clinical & Coding Specifications
Clinical Context
A 62-year-old patient with persistent cytopenias and peripheral blood smear abnormalities is evaluated by a hematologist. Bone marrow biopsy suggests a myelodysplastic/myeloproliferative neoplasm. A molecular diagnostic test for U2AF1 hotspot variants (for example S34F, S34Y, Q157R, Q157P) is ordered on a peripheral blood or bone marrow specimen to inform diagnosis, prognosis, and therapeutic decision-making. The laboratory accessioning staff receives the specimen, assigns a unique identifier, and the molecular pathology/lab medicine team performs DNA extraction, targeted sequencing or allele-specific assay, and bioinformatic analysis. The lab analyst performs the technical testing and generates a report documenting detected U2AF1 variants, allele frequencies, and interpretive comments for the ordering hematologist. Typical sites of service include hospital outpatient laboratories, independent reference laboratories, and hospital inpatient laboratories. The specimen type is usually peripheral blood or bone marrow aspirate. Results may influence classification of hematologic malignancy, prognosis, and eligibility for targeted clinical trials or specific treatment strategies.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | Use when billing physician interpretation separately from the lab technical component, if applicable. |