Summary & Overview
CPT 81276: KRAS Non-Exon 2 Variant Detection
CPT code 81276 represents a molecular diagnostic laboratory test that detects KRAS gene variants outside of exon 2. This assay provides technical laboratory analysis used in tumor genotyping to identify actionable or prognostic non-exon 2 KRAS mutations. Nationally, such tests are important for precision oncology workflows because they can influence targeted therapy decisions, clinical trial eligibility, and prognostic assessment across multiple cancer types.
Key payers discussed include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of clinical context for KRAS non-exon 2 variant testing, common payer coverage categories, and the types of benchmarks and policy elements typically monitored for molecular pathology codes. The publication covers where this service is typically performed (clinical and reference molecular laboratories), the service line classification (molecular/genetic testing), and how this CPT code fits into laboratory workflow as the technical component of KRAS variant detection.
The report also outlines typical documentation expectations, common modifiers seen on claims for laboratory technical services, and items labeled Data not available in the input where specific pricing, taxonomies, ICD-10 linkage, and payer-specific policies were not provided. This national-level summary is intended to orient clinicians, laboratory managers, and billing professionals to the clinical role and billing context of CPT code 81276.
Billing Code Overview
CPT code 81276 describes a technical laboratory test that detects the presence of additional variants in the KRAS (Ki‑ras2 Kirsten rat sarcoma viral oncogene) gene outside of exon 2. The service is a molecular diagnostic assay that identifies non-exon 2 KRAS variants to inform tumor genotyping and potential targeted therapy selection.
Service type: Molecular pathology / targeted genotyping (technical component)
Typical site of service: Clinical molecular laboratory, hospital laboratory, or reference diagnostic laboratory
Clinical & Coding Specifications
Clinical Context
A 62-year-old patient with advanced colorectal adenocarcinoma undergoes tumor genomic profiling after progression on first-line therapy. The oncologist orders KRAS mutation analysis beyond exon 2 to detect less common activating variants that can impact targeted therapy selection. A pathology/laboratory requisition is placed for 81276 and a formalin-fixed, paraffin-embedded tumor block or circulating tumor DNA sample is sent to a molecular diagnostics lab. The laboratory analyst performs targeted sequencing or PCR-based methods to detect additional KRAS variants outside exon 2; results are reported in the pathology report and routed to the ordering oncologist. Typical site of service is a clinical molecular diagnostics laboratory within a hospital-based lab or independent reference laboratory. The workflow includes specimen accessioning, DNA extraction, assay setup, analytic run, result interpretation by a molecular pathologist, and final report release to the ordering provider.
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | When the interpreting molecular pathologist bills separately for result interpretation and report generation. |
TC | Technical component | When the performing laboratory bills for the technical testing only (instrumentation and reagents). |
90 | Reference (outside) laboratory | When testing is performed by an outside reference laboratory and billing reflects that relationship. |
91 | Repeat clinical diagnostic test | When the test is repeated on the same patient for verification or confirmatory purposes within a defined interval. |
59 | Distinct procedural service | When multiple molecular tests are reported on the same date and Modifier 59 indicates distinct services not normally billed together. |
52 | Reduced services | When the assay is partially completed or performed at a reduced level of service. |
53 | Discontinued procedure | When testing is started but discontinued for clinical or technical reasons prior to completion. |
78 | Unplanned return to the operating/procedure room by the same physician following initial procedure | Rare for molecular testing; used if an additional specimen is obtained intra-procedurally and additional testing is billed. |
80 | Assistant surgeon | Not typically used for lab tests; included when a surgical assistant's service results in a specimen that prompts additional billing actions. |
62 | Two surgeons | Uncommon for molecular lab billing; used when two surgeons are involved in obtaining the specimen that leads to testing. |
22 | Increased procedural services | When complexity or additional steps in the molecular assay justify reporting increased procedural services. |
59 | Distinct procedural service | (Note: 59 listed earlier; use per guidance to indicate distinct test when NOC edits apply.) |
XU | Unusual non-overlapping service (X modifier) | When a laboratory service is distinct and separate from other services on the same day under NCCI X{EPSU} subset rules. |
| Taxonomy Code | Specialty | Notes |
|---|---|---|
| 207RR0500X | Molecular Pathology | Laboratory specialists who interpret molecular diagnostic assays. |
| 207RG0300X | Clinical Molecular Genetics | Providers focused on genetic testing and molecular diagnostics. |
| 207L00000X | Pathology | Anatomic and clinical pathologists overseeing laboratory testing and reporting. |
| 207LP2900X | Hematopathology | When hematologic malignancies prompt KRAS testing or oversight of molecular assays. |
| 207N00000X | Oncology | Medical oncologists who order molecular testing to guide systemic therapy. |
Related Diagnoses
| ICD-10 Code | Description | Clinical Relevance |
|---|---|---|
C18.9 | Malignant neoplasm of colon, unspecified | Colorectal adenocarcinoma frequently undergoes KRAS testing to guide therapy and prognosis. |
C19 | Malignant neoplasm of rectosigmoid junction | Tumors in this location are part of colorectal cancer workup where KRAS mutation status is relevant. |
C20 | Malignant neoplasm of rectum | Rectal cancers are routinely tested for KRAS variants to inform anti-EGFR therapy decisions. |
C80.1 | Malignant (primary) neoplasm, unspecified, with metastasis | Metastatic colorectal cancer commonly prompts extended KRAS testing beyond exon 2 for treatment selection. |
D37.4 | Neoplasm of uncertain behavior of colon | When neoplastic behavior is uncertain, molecular profiling may be used to clarify biology and risk. |
Related CPT Codes
| CPT Code | Description | Relationship to This Procedure |
|---|---|---|
81275 | KRAS (Kirsten rat sarcoma viral oncogene) gene analysis; detection of variants in exon 2 (codons 12 and 13) | Commonly performed prior to or alongside 81276; exon 2 testing covers the most frequent KRAS variants and may be ordered first. |
81479 | Unlisted molecular pathology procedure | Used when a specific, uncommon KRAS variant panel or novel testing method is performed that is not otherwise coded. |
88360 | Immunohistochemistry, tissue; per specimen; initial single antibody stain | May be performed on tumor tissue to characterize tumor markers before molecular testing. |
88342 | Molecular morphology; interpretation and report | Used when molecular pathology interpretation with morphologic correlation is reported alongside sequencing results. |
0000U | (Example) — Proprietary or lab-developed test CPT Category II/III codes may apply depending on assay | Some laboratories use proprietary CPT codes for specific next-generation sequencing panels that include KRAS coverage; billed with relation to 81276 when broader panels are run. |
Note: If a code listed above is not available in a payer's fee schedule, the appropriate alternative or unlisted molecular pathology code may be used according to payer policy.