General Genetic Testing, Somatic Disorders
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Defines Avalon Healthcare Solutions coverage policy for somatic (tumor) genetic testing when no condition-specific policy exists; governs diagnostic, prognostic, and therapeutic use of somatic genomic tests for members covered by AHS benefit plans.
Added CPT code 81524 (effective date 1/1/2026) to the policy coding list.
Added CPT code 0172U to the policy coding list.
Added CPT codes 81449 and 81456 and HCPCS 0523U (effective date 1/1/2025).
Off-cycle coding modification: Added CPT code 0444U (effective date 4/1/2024).
Clarified Avalon's definition of a genetic panel in reimbursement policy R2162, with a note about two or more gene tests run on the same platform.
Coverage Criteria
Covered indications
Covered when ANY of the following conditions are met
Documented clinical utility required.
Not medically necessary / Not covered
Not covered
Requests for testing outside covered indications will be denied.
Guideline-based coverage criteria
Guideline-derived recommendations for when somatic and germline testing should be performed
Based on ASCO guidance (see references).
ASCO provisional clinical opinion (2022).
ESMO and British Sarcoma Group recommendations.
Medically Necessary When Guideline-Indicated
Coverage supported when testing is used to inform diagnosis or therapy selection according to guideline recommendations
References: ESMO, BSG, AUA/ASTRO/SUO, ASCO and related guidelines.
Therapy-Directed Requirement (GIST)
Testing required prior to targeted systemic therapy in certain contexts
British Sarcoma Group guidance; confirm diagnosis by experienced pathologist and accredited laboratory testing before imatinib.
Coverage criteria status
Coverage criteria unchanged after review
See revision history for coding updates unrelated to criteria.
Somatic (tumor) genetic testing is covered when it is used to inform clinical care in one of two situations: (1) testing for a specific somatic mutation or mutations that have documented clinical utility for diagnosis, selection of therapy, or prognostication; or (2) repeat testing performed for recurrence monitoring or when newly arisen alterations could reasonably change non-investigational therapy (for example, would lead to addition, elimination, or alteration of therapy). Documentation must demonstrate the identified mutation(s) have the required clinical utility to meet coverage criteria.
The policy does not list discrete exclusions by test name in the excerpted guidance; however, professional society guidance (ASCO and related statements) recommends that multigene panel testing be used only when clinically justified — for example, when more than one biomarker-linked therapy is approved for the disease or when site-agnostic approvals (e.g., high TMB, dMMR, NTRK) provide a rationale for broad testing. Ordering clinicians should document the rationale for panel testing in the clinical record.
ESMO guidance identifies that BRCA germline and somatic mutation testing and HRD assessment are supported to identify patients likely to benefit from PARP inhibitors in high-grade serous ovarian carcinoma, but states there is insufficient evidence to establish clinical validity for panels of non-BRCA HRR genes or for BRCA1 or RAD51C promoter methylation to predict PARP inhibitor benefit. Such broader non-BRCA HRR panels or promoter methylation assays are therefore not supported by the cited guideline evidence for this purpose.
The provided excerpt does not list any additional explicit exclusions. The revision history confirms literature review did not change coverage criteria and documents coding updates, but does not add new exclusionary language in the reviewed sections.
Any somatic genetic testing (single-gene or multi-gene panel) that does not meet the covered indications described in this policy (diagnosis/therapy/prognostication with documented clinical utility, or the specified repeat-testing situations) does not meet coverage criteria and will be considered not medically necessary.
The document excerpt does not provide a formal definition of 'not medically necessary' (NMN) conditions beyond the general statements above, but emphasizes that multigene panel use should be targeted to scenarios with clinical justification — e.g., when multiple biomarker-linked therapies exist or when site-agnostic indications support broader testing. Where clinical utility or guideline support is lacking, panel testing may be considered NMN.
The policy notes that panel testing of non-BRCA HRR genes and assays such as BRCA1 or RAD51C promoter methylation lack sufficient evidence to predict PARP inhibitor response per ESMO guidance; such tests for the purpose of predicting PARPi benefit are therefore not supported by the guideline evidence cited in this policy.
Within the supplied excerpt there are no explicit statements labeling specific tests as 'not medically necessary.' The review/revision history documents coding additions and clarifications but does not introduce new explicit NMN statements in this section.
Covered Indications (Specific Clinical Contexts)
Diagnosis, selection of therapy, or prognostication when the presence of specific somatic mutation(s) has documented clinical utility.
Covered when ALL of the following are met:
Documentation of clinical utility required in the medical record.
Per guideline recommendations, testing should be performed in a certified/accredited laboratory.
Repeat testing for recurrence or to identify alterations that would change non-investigational therapies is included.
Repeat testing for recurrence monitoring or when new alterations could change non-investigational therapy.
Covered when ANY of the following conditions are met
Meets coverage criteria when used for recurrence monitoring.
Meets coverage criteria when test results would change clinical management.
Germline and/or somatic testing for patients with ovarian cancer (including epithelial ovarian cancer) to assess BRCA1/2 and homologous recombination deficiency.
Covered when ALL of the following are met:
ASCO and ESMO guidance support germline and somatic BRCA testing and HRD assessment.
Genomic sequencing for metastatic or advanced solid tumors when specific genomic alterations will guide treatment decisions.
Covered when ALL of the following are met:
ASCO provisional opinion recommends sequencing in certified labs when results will guide therapy.
Mutational analysis for gastrointestinal stromal tumors (GIST) to detect KIT and PDGFRA mutations.
Covered when ALL of the following are met:
ESMO and BSG recommend mutational analysis as standard practice in GIST work-up.
Diagnostic confirmation and therapy selection in GIST (KIT/PDGFRA testing) and identification of BRCA germline/somatic mutations in high-grade serous ovarian carcinoma for PARP inhibitor therapy.
Covered when ALL of the following are met:
Guideline-supported indications for diagnostic confirmation and therapy selection.
Somatic molecular testing in metastatic castration-resistant prostate cancer to identify DNA repair deficiency mutations and MSI status for prognosis and targeted therapy selection.
Covered when ALL of the following are met:
AUA/ASTRO/SUO and EAU-related guidance recommend germline and somatic testing in mCRPC.
Somatic tumor genomic testing to inform therapeutic decision-making in advanced or metastatic solid tumors (guideline-supported contexts referenced).
Covered when ALL of the following are met:
ASCO, NCCN, ESMO and other guideline references cited in policy support these contexts.
Eligibility Requirements
No family-history-based eligibility criteria are specified in these excerpts. The policy text and guideline citations note that family history can inform the selection of testing (particularly germline testing), but the policy does not impose explicit family history requirements for somatic testing in the sections reviewed.
0 top-level nodes
ASCO and other guideline statements referenced in the policy discuss timing of somatic BRCA1/2 testing in ovarian cancer. ASCO and related guidance recommend offering germline and somatic BRCA testing (including HRD measures) and indicate somatic testing may be performed at diagnosis or as soon as feasible; some guidance suggests somatic BRCA1/2 testing may be reserved or sequenced around recurrence in selected circumstances, and sequential somatic testing may be offered after prior uninformative tests.
0 top-level nodes
0 top-level nodes
Not Covered / Limitations
Somatic genetic testing for indications that do not meet the policy's covered criteria (diagnostic/therapeutic/prognostic utility or specified repeat testing) is not covered and may be denied as not meeting coverage criteria.
The excerpt does not include an explicit enumerated list of specific tests that are categorically not covered. Denials generally follow from tests not meeting the coverage criteria described elsewhere in the policy.
The policy and cited ESMO guidance indicate insufficient evidence supports use of panels of non-BRCA HRR genes or BRCA1/RAD51C promoter methylation testing to predict PARP inhibitor response; use of these assays for that purpose is therefore unsupported and may be considered not covered.
The provided excerpt does not specify any additional explicit exclusions or tests that are categorically excluded from coverage beyond the general criteria-based exclusions described in other sections.
Coding and Procedure Codes
| 81168 | CCND1/IGH (t(11;14)) (eg, mantle cell lymphoma) translocation analysis, major breakpoint, qualitative and quantitative, if performed. |
| 81191 | NTRK1 (neurotrophic receptor tyrosine kinase 1) (eg, solid tumors) translocation analysis. |
| 81192 | NTRK2 (neurotrophic receptor tyrosine kinase 2) (eg, solid tumors) translocation analysis. |
| 81193 | NTRK3 (neurotrophic receptor tyrosine kinase 3) (eg, solid tumors) translocation analysis. |
| 81194 | NTRK (neurotrophic-tropomyosin receptor tyrosine kinase 1, 2, and 3) (eg, solid tumors) translocation analysis. |
| 81233 | BTK (Bruton's tyrosine kinase) (eg, chronic lymphocytic leukemia) gene analysis, common variants (eg, C481S, C481R, C481F). |
| 81261 | IGH@ (Immunoglobulin heavy chain locus) (eg, leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (eg, polymerase chain reaction). |
| 81262 | IGH@ (Immunoglobulin heavy chain locus) (eg, leukemias and lymphomas, B-cell), gene rearrangement analysis to detect abnormal clonal population(s); direct probe methodology (eg, Southern blot). |
| 81305 | PDGFRA variant gene analysis (eg, gastrointestinal stromal tumor [GIST]), targeted sequence analysis (eg, exons 12, 18). |
| 81405 | Targeted cytogenomic array analysis. |
| 81449 | Solid organ or hematolymphoid neoplasm panel, 51 or greater genes, genomic sequence analysis panel, interrogation for sequence variants and copy number variants or rearrangements, if performed; RNA analysis. |
| 0523U | Oncology (solid tumor), DNA, qualitative NGS of single-nucleotide variants (SNV) and insertion/deletions in 22 genes utilizing formalin-fixed paraffin-embedded tissue; reported as presence or absence of mutation(s) (proprietary oncoReveal CDx, Pillar Biosciences). |
| 81599 | Unlisted multianalyte assay with algorithmic analysis. |
| 81524 | CPT code added to policy (81524) (added per revision history; specific description not provided in excerpt). |
| 0172U | Category I/III code 0172U added to policy (added per revision history; specific description not provided in excerpt). |
| 81449 | CPT code 81449 added to policy (added per revision history; specific description not provided in excerpt). |
| 81456 | CPT code 81456 added to policy (added per revision history; specific description not provided in excerpt). |
| 0523U | HCPCS/temporary code 0523U added to policy (effective 1/1/2025) (specific description not provided in excerpt). |
| 0444U | CPT/temporary code 0444U added off-cycle (effective 4/1/2024) (specific description not provided in excerpt). |
Provider Actions and Operational Notes
Verify benefits and obtain prior authorization if required
Application of coverage criteria depends on the member's individual benefit coverage at time of the request; prior authorization may be required per member benefits and applicable Medicare/Medicaid specifications.
Use certified laboratories for therapy-directed sequencing
Order tumor genomic sequencing through a certified/accredited laboratory when specific genomic alterations will guide treatment selection; consider regulatory approvals and clinical utility when selecting the assay.
Prior authorization may be required for large panels and proprietary tests
Certain large multigene somatic panels and proprietary/CLIA tests (examples include solid organ neoplasm panels and listed proprietary tests such as oncoReveal/myChoice) are associated with CPT/HCPCS codes and may require prior authorization per payer rules.
Be aware of recent coding additions that may affect workflows
Coding updates have added specific CPT/HCPCS codes to the policy (e.g., 81524, 0172U, 81449, 81456, 0523U, 0444U); these additions may affect prior authorization workflows though the policy excerpt does not specify new authorization steps tied to these codes.
Refer to AHS-R2162 when multiple tests run on one platform
If two or more gene tests are run on the same platform, follow the AHS-R2162 Reimbursement Policy for reimbursement rules.
Obligatory mutational analysis before neoadjuvant imatinib in GIST
Perform mutational analysis (e.g., KIT/PDGFRA testing) prior to planned neoadjuvant imatinib for GIST because certain mutations (such as PDGFRA exon 18 D842V) predict insensitivity and would change therapy selection.
No unspecified provider action
No specific additional provider action is specified in the excerpt.
Document clinical utility to support medical necessity
Provide documentation demonstrating clinical utility: show that identified mutation(s) have documented benefit for diagnosis, therapy selection, or prognostication; for repeat testing, document that testing is for recurrence monitoring or that new alterations would change non-investigational therapy.
- Include rationale linking the requested test to diagnosis, therapy selection, prognostication, or recurrence monitoring.
- For repeat testing, document expected impact on non-investigational therapy.
Require pathology confirmation and accredited laboratory testing
Ensure pathology evaluation of tumor tissue specimens and use an accredited laboratory for mutational analysis; for GIST, diagnosis should be established by an experienced pathologist using immunohistochemistry and molecular analysis performed by an accredited laboratory.
- Confirm histopathologic diagnosis (IHC) before molecular testing when planning targeted therapy.
- Send testing to accredited/certified laboratories.
Perform pathology review and use accredited labs for somatic testing
Pathology evaluation of tumor tissue specimens must be performed for assessment of somatic molecular alterations, and mutational analysis should be performed by an accredited laboratory as part of diagnostic work-up when indicated.
Revision history: coding and panel-definition notes (no new documentation required)
The revision history documents coding additions and clarifying notes about definitions of panels; no new documentation requirements are specified in the update.
Denial risk for tests not meeting covered indications
Requests for somatic genetic testing that are not for diagnosis, selection of therapy, prognostication with documented clinical utility, or specified repeat testing will be denied as they do not meet coverage criteria.
Avoid panel testing without biomarker-linked rationale
Ordering multigene panel testing without a rationale tied to approved biomarker-linked therapies or site-agnostic indications (e.g., high TMB, dMMR, NTRK) may increase risk of inappropriate testing and potential denial; ASCO advises panel testing when more than one biomarker-linked therapy is approved or site-agnostic approvals provide rationale.
Claims may be denied if they conflict with government coverage determinations
If a claim conflicts with applicable local, state, or federal determinations (for example, LCDs/NCDs for Medicare), it may be denied; government policy supersedes this policy when conflicts exist.
No change to coverage criteria after literature review; coding updated
Literature review did not necessitate modifications to coverage criteria, though coding changes were made during review.
No explicit genetic counseling requirement in policy excerpt
The policy does not state explicit pre- or post-test genetic counseling requirements in this excerpt.
Offer germline testing and counseling where guideline-recommended
Offer germline testing and counseling regarding family risk in contexts where guidelines recommend it (e.g., metastatic castration-resistant prostate cancer per AUA/ASTRO/SUO).
Specialist-directed ordering is implied though not mandated
The excerpt does not specify ordering-provider restrictions; however, guidelines and clinical context imply that specialists (oncologists, pathologists) are central to appropriate test ordering and interpretation.
Begin testing within specialist evaluation
Initiate testing in the context of specialist evaluation (for example, a pathologist experienced in GIST diagnosis or the treating oncologist) to ensure appropriate biopsy technique and test selection.
Use oncology guideline recommendations to guide ordering and timing
Guideline citations (ASCO, NCCN, ESMO and others) are provided in support of oncologist-directed sequencing in many contexts; use these guideline recommendations to guide test ordering and timing.
Background and Evidence
Somatic mutations are genetic alterations that arise after conception and are present in non-germline cells; they commonly occur in neoplasms and include single nucleotide variants, insertions/deletions, copy number variants, structural variants, and gene fusions. Molecular profiling of tumors (e.g., NGS, comprehensive genomic profiling) is used clinically to aid diagnosis, prognostication, and selection of targeted therapies when actionable alterations with demonstrated clinical utility are identified.
Definitions
Provider-Facing Coding Notes
Revision History and Policy Changes
Reviewed and updated background, guidelines, and references; literature review did not change coverage criteria; added CPT code 81524 (effective 2026-01-01) and code 0172U to the policy coding list.
Added CPT codes 81449 and 81456 and HCPCS code 0523U (effective 2025-01-01) and clarified the policy note defining genetic panels (refer to AHS-R2162 for multiple tests on same platform).
Off-cycle coding modification: added CPT/temporary code 0444U (effective 2024-04-01).
Initial policy implementation recorded (policy effective date noted in revision history).
The 05/01/2026 literature review concluded that coverage criteria did not require modification. The revision history documents coding additions (including addition of CPT codes such as 81524 and other temporary codes) and clarifying edits to panel definitions, but did not change the policy's coverage rules.
Revision notes record administrative and coding updates (for example additions of CPT/HCPCS codes and a clarified note referring to AHS-R2162 for reimbursement rules when two or more gene tests are run on the same platform). These changes are procedural/coding in nature; the excerpt does not impose new documentation requirements.
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