A tumor-only sequencing panel comes back on a 58-year-old woman with metastatic ovarian cancer. The lab ran it to find an actionable driver, somatic alterations the oncologist could target with therapy. Buried in the report is a BRCA1 variant. Now there is a question the test was never designed to answer cleanly: is that variant something the tumor acquired, or is it inherited, sitting in every cell of her body and, by extension, possibly in her sister's and her daughter's? The honest answer from a tumor-only assay is often "we can't tell from this alone." And that single ambiguity is where two entirely separate Medicare coverage frameworks collide.
Disclaimer: This article is educational and is not medical, legal, or billing advice, and it is not a coverage determination for any specific patient or claim. Coverage policies change, Medicare Administrative Contractors apply local policies, and the only authoritative sources are the current NCD and applicable LCD language. Always verify against CMS's current policy and consult qualified clinical, billing, and compliance professionals before making coverage, treatment, or reimbursement decisions. Use this information at your own risk.
Two tests that answer two different questions
The clinical distinction is clean, even if the reimbursement consequences are not.
Somatic testing looks for acquired mutations, the genetic changes that arose within a tumor as it developed. These variants are specific to the neoplasm and are not present in the patient's normal cells. The clinical question is forward-looking and therapeutic: what is driving this cancer, and what can we do about it? Somatic profiling is how oncologists find targetable alterations, fusions such as ALK, ROS1, NTRK, or RET, mutations such as BRAF or KRAS, amplifications such as HER2, and signals such as microsatellite instability, mismatch-repair deficiency, or tumor mutational burden, that point toward a specific therapy or a clinical trial.
Germline testing looks for inherited mutations. Because a germline variant is present in the fertilized egg, it appears in every cell of the body, which is why it can be detected from blood or saliva rather than tumor tissue. The clinical question is different in kind: does this patient carry a hereditary predisposition that affects their lifetime risk, their surgical and surveillance choices, their eligibility for certain therapies, and the risk borne by their blood relatives? A germline BRCA1 finding is not just about today's tumor; it is a fact about the family.
The two are not competitors. A complete picture of a cancer patient often requires both, and the design of Medicare's coverage rule explicitly anticipates that clinicians may order somatic and germline testing together. The friction is not clinical. It is that Medicare reaches the two through different doors.
The shared roof: NCD 90.2
Both somatic and germline next-generation sequencing for cancer live under the same national rule, National Coverage Determination 90.2, Medicare's framework for covering NGS as a diagnostic laboratory test in patients with cancer. It was finalized in March 2018 and amended effective January 27, 2020. The NCD is explicit that its criteria apply to NGS tests of both somatic and germline mutations, so it would be easy to assume one set of conditions governs everything.
It does not work that way. NCD 90.2 is better understood as one roof over two rooms. The baseline conditions are shared, the test must be performed in a CLIA-certified laboratory, ordered by the treating physician, with results furnished to that physician to guide management, and the patient must not be receiving a repeat of the same NGS test for the same genetic content. But the gating clinical criterion differs depending on whether the test is somatic or germline, and that is the part that decides which medical-necessity narrative a claim has to tell.
Two coverage pathways inside one rule
The somatic pathway is tied to disease burden. Under NCD 90.2, somatic NGS is covered for a patient who has recurrent, relapsed, refractory, or metastatic cancer, or advanced stage III or IV cancer, and who has decided to seek further cancer treatment. There is a cleaner sub-path within this: when an NGS assay is FDA-approved or cleared as a companion in vitro diagnostic and is used for an indication matching the patient's cancer, NCD 90.2 provides a defined national coverage route. FDA companion-diagnostic standing is the most predictable way to Medicare coverage for a somatic assay precisely because it removes ambiguity about whether the test is reasonable and necessary for that cancer. Tests without that standing can still be covered, but coverage shifts to the Medicare Administrative Contractor's discretion, which is where the MolDX program and its Local Coverage Determinations do much of the real work.
The germline pathway was added by the 2020 amendment and is built on hereditary-risk logic rather than disease stage. Effective for services on or after January 27, 2020, CMS determined that germline NGS is covered nationally when the patient has a clinical indication for germline testing for hereditary breast or ovarian cancer and a risk factor for inherited breast or ovarian cancer, and has not previously had the same germline NGS test for the same genetic content. Note what is absent from that pathway: there is no requirement for stage III/IV or metastatic disease. The germline question is about heredity, not tumor burden, so the criteria track family history, personal history, and clinical risk features rather than how advanced the cancer is. For germline tests beyond the FDA-approved national list, and for cancers other than breast and ovarian, contractors may again set local coverage when the patient has a clinical indication and risk factor for inherited cancer.
The practical upshot: the documentation that proves "this patient has stage IV disease and is pursuing treatment" is not the documentation that proves "this patient has a personal and family history suggestive of a hereditary syndrome." Same NCD, different stories.
Somatic vs. germline at the coverage level
| Somatic testing | Germline testing | |
|---|---|---|
| What it tests | Acquired mutations in tumor tissue; not present in normal cells | Inherited mutations present in every cell; detectable from blood or saliva |
| Clinical question | What is driving this tumor and how should it be treated? | Does the patient carry a hereditary cancer predisposition affecting them and their relatives? |
| Medicare framework | NCD 90.2 somatic pathway: generally tied to recurrent/relapsed/refractory/metastatic or advanced stage III/IV cancer, or an FDA-approved companion diagnostic; non-CDx tests fall to MAC/MolDX discretion | NCD 90.2 germline pathway (2020 amendment): clinical indication and risk factor for hereditary breast or ovarian cancer; not stage-dependent; contractor discretion for other cancers |
| Typical medical-necessity narrative | Advanced/metastatic disease status; intent to pursue therapy; targetable biomarker relevant to treatment selection | Personal/family history and clinical risk features suggestive of a hereditary syndrome; result informs risk management and relatives |
| Representative CPT family | Solid-tumor genomic sequencing panels (for example, the 5–50 gene and 51-or-greater somatic panel codes) | Hereditary cancer syndrome panel codes (for example, the breast/ovarian-related hereditary panel codes) |
Reference the CPT families above by concept; the exact code that applies depends on the assay, the genes, and current code definitions, which change. The point of the table is not the code numbers. It is that the column a test belongs in determines almost everything downstream, the eligible patient profile, the necessity language, and the framework a reviewer will measure the claim against.
Where it gets genuinely hard: one sample, two frameworks
Return to the opening case. Tumor-only sequencing is, by design, run on tumor tissue without a matched normal sample. That makes it efficient for finding somatic drivers, but it also means the assay detects any variant present in the tumor cells, including inherited ones, and generally cannot distinguish somatic from germline on its own. A BRCA1 variant on a tumor-only report may be somatic, or it may be the tip of a hereditary syndrome. The literature is direct about this: tumor-only sequencing can mistakenly attribute germline variants to the tumor, and confirming a suspected germline finding usually requires a separate, dedicated germline test on a blood or saliva sample.
That confirmatory test does not inherit the somatic test's coverage. It is evaluated under the germline pathway, with its own clinical-indication-and-risk-factor narrative. So a single sequencing event can implicate both rooms under NCD 90.2's roof: the original tumor panel under the somatic pathway, and the reflex germline confirmation under the germline pathway. Payers have noticed this sequence too; commercial utilization-management policies now specifically address hereditary (germline) testing performed after tumor (somatic) testing, with their own criteria for when the follow-on germline test is warranted. The blood draw or biopsy may be one physical thing. The coverage logic is two.
This is also where claims quietly fail. A germline panel billed as though stage IV disease were the qualifying criterion misses the point of the germline pathway entirely, hereditary risk, not tumor burden, is what makes it reasonable and necessary. A tumor panel whose documentation leans on family history rather than advanced-disease status and treatment intent tells the wrong story for the somatic pathway. In both directions, the test might have been coverable under its framework, yet gets denied because the claim was matched to the wrong one.
The strategic takeaway
The clean lesson here is that "covered by Medicare" is never a single fact about a test. It is a fact about a test plus an indication plus a framework. Somatic and germline assays share a national rule and can share a patient and even a sample, but they are reached through different coverage pathways with different gating criteria and different medical-necessity narratives. Matching each claim to the correct pathway, and documenting to that pathway's criteria, is the difference between a covered test and a paid one.
That per-test, per-indication coverage logic is precisely the layer that is easy to get wrong and easy to fall out of date on, because the NCD, the FDA companion-diagnostic list, and the MolDX LCDs all keep moving. Keeping that rule layer accurate, knowing which framework governs which test for which indication across payers, is exactly what Converus is built to track. The frameworks will keep evolving; what should not change is your ability to send each claim through the right door.
Sources
- NCD - Next Generation Sequencing (NGS) (90.2) — Centers for Medicare & Medicaid Services, Medicare Coverage Database (finalized March 2018; amended effective January 27, 2020). Establishes that criteria apply to both somatic and germline mutations, the advanced-cancer somatic criteria, the FDA companion-diagnostic pathway, and the germline hereditary breast/ovarian pathway.
- NCA - Next Generation Sequencing (NGS) for Medicare Beneficiaries with Advanced Cancer (CAG-00450R) Decision Memo — CMS decision memo underlying the 2020 germline amendment.
- CMS finalizes coverage of Next Generation Sequencing tests, ensuring enhanced access for cancer patients — CMS press release describing somatic actionable-mutation coverage and companion-diagnostic application to advanced cancer.
- CMS to Cover FDA-Approved, -Cleared NGS Germline Tests for Breast, Ovarian Cancer Patients — GenomeWeb coverage of the January 2020 germline expansion and its clinical-indication-and-risk-factor criteria.
- LCD - MolDX: Next-Generation Sequencing for Solid Tumors (L38158) and MolDX: Repeat Germline Testing (L38351) — MolDX Local Coverage Determinations distinguishing somatic (tumor) from germline (inherited) testing and contractor-level coverage.
- A Clinical Approach to Detecting Germline Pathogenic Variants From Tumor-Only Sequencing and Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing — peer-reviewed sources on tumor-only sequencing surfacing incidental germline variants and the inability to distinguish somatic from germline without a matched normal.
- Hereditary (Germline) Testing After Tumor (Somatic) Testing — eviCore utilization-management guideline addressing follow-on germline testing after somatic testing.
- Billing and Coding: Genetic Testing for Oncology (A59125) — CMS billing/coding article referencing somatic and hereditary (germline) panel CPT families.