CurrentUnitedHealthcarePolicy 2025T0009RR

Genetic Testing for Hereditary Cancer

Coverage policy for genetic and molecular testing to assess hereditary cancer risk, specifying when single-gene, known-mutation, and multi-gene panel testing (including BRCA1/2) are considered medically necessary for members and when tests are unproven/not covered.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer

Policy CodePolicy 2025T0009RR

Change TypeNo material changes

Effective DateMay 1, 2025

Next Review Date

Key ActionDocument a pedigree and include personal and family history, tumor dMMR or tumor genomic findings, and relevant risk-model scores when requesting genetic testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

5-10%hereditary cancers (est.)

60-72%BRCA1 breast risk

55-69%BRCA2 breast risk

20+adenomas threshold

13.3%PGV detection (study)

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Lynch Syndrome (LS) Testing Criteria

Lynch Syndrome (LS) testing is included within criteria for hereditary colorectal and endometrial cancer evaluation. The following criteria specify when germline testing for LS (MMR genes: MLH1, MSH2, MSH6, PMS2, and EPCAM 3' deletions) is considered proven and medically necessary or when testing should be considered.

ANY of the following

Known family variant
- There is a known Lynch syndrome pathogenic/likely pathogenic (P/LP) variant in the family.
Personal history of LS-related cancer
- - Diagnosed at age < 50 years.
  - Tumor demonstrates dMMR (MSI-high by PCR/NGS or abnormal MMR IHC) at any age.
  - Synchronous or metachronous LS-related cancer(s) at any age.
  - Personal history of another LS-related cancer (see clinical guidance).
Family history criteria
- Individual has a first- or second-degree relative with an LS-related cancer diagnosed at age < 50 years.
- Individual has two or more first- or second-degree relatives with LS-related cancers regardless of age.
Extended family history thresholds
- - One or more first-degree relatives with CRC or EC diagnosed < 50 years.
  - One or more first-degree relatives with CRC or EC and a synchronous or metachronous LS-related cancer at any age.
  - Two or more first- or second-degree relatives with LS-related cancers with at least one diagnosed < 50 years.
  - Three or more first- or second-degree relatives with LS-related cancers at any age.
Predictive model or score
- Individual has a predictive model score ≥ 5% for a germline MMR P/LP variant (e.g., PREMM5, MMRpro, MMRpredict).
- Note: Individuals with a personal history of CRC and/or EC and a PREMM5 score ≥ 2.5% should be considered for multigene panel testing; for unaffected individuals and clinical judgment may allow use of a ≥ 2.5% threshold to select candidates for MMR testing.
Tumor and tumor-to-germline indications
- Personal history of a tumor with dMMR (MSI-high or abnormal MMR IHC) diagnosed at any age.
- Personal history of a P/LP variant detected on tumor genomic testing that has clinical implications if also detected in the germline.
Consideration for individuals ≥50–49+
- Testing may be considered for individuals with a personal history of CRC or EC diagnosed at age ≥ 50 years who are untested for tumor dMMR status or have documented absence of dMMR in the tumor; clinical judgment should guide testing decisions.

Specific Covered Indications and Syndrome-based Testing

Recommended germline testing considerations by tumor type

Recommended germline gene consideration by tumor type (professional society guidance):

Endometrial cancer: More strongly recommended genes include EPCAM, MLH1, MSH2, MSH6, PMS2, PTEN, and STK11.

Gastric cancer: More strongly recommended genes include APC, CTNNA1, EPCAM, MLH1, MSH2, MSH6, PMS2, BMPR1A, CDH1, SMAD4, and STK11.

Gastrointestinal stromal tumors (GIST): More strongly recommended genes include KIT and PDGFRA; if SDH‑deficient or SDH‑mutant tumor then SDHA, SDHAF2, SDHB, SDHC, SDHD; if NF1‑mutated tumor then NF1.

Non‑small cell lung cancer: More strongly recommended genes include EGFR and STK11; less strongly recommended: TP53.

Epithelial ovarian cancer: More strongly recommended genes include BRCA1, BRCA2, BRIP1, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D; less strongly recommended: ATM.

Pancreatic adenocarcinoma: More strongly recommended genes include ATM, BRCA1, BRCA2, CDK4, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53; NCCN recommends germline testing with comprehensive panels for any confirmed pancreatic cancer.

Pheochromocytomas and paragangliomas: More strongly recommended genes include FH, MAX, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, NF1, and VHL.

Prostate cancer: If criteria met, germline multigene testing should include at least BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.

Tumor‑detected pathogenic variants prompting germline testing: When tumor testing reveals pathogenic variants in listed genes (e.g., BRCA1/2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C, RAD51D, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC2, VHL, APC, PTEN, RB1, TP53 if patient <30), germline testing should be offered regardless of other criteria.

Considered/Optional germline testing recommendations

Genes where tumor findings may prompt consideration or where testing may be offered:

Genes where tumor testing may prompt germline testing: If tumor testing indicates pathogenic variants in genes such as ATM, BAP1, BARD1, CHEK2, DICER1, FH, FLCN, NF1, POLD1, POLE, SDHA, CDKN2A, or SMARCA4 (and others listed for young patients), germline testing may be offered and should be interpreted with counseling and expert input.

Gene–tumor specificity and counseling: ASCO emphasizes tumor‑ and gene‑specific relevance (e.g., ATM relevant to breast, gastric, ovarian, pancreatic, prostate; BAP1 to melanoma, renal cell, mesothelioma) and recommends genetic counseling and expert interpretation when offering germline testing based on tumor findings.

Eligibility Requirements and Known-Familial Mutation Testing

Coverage eligibility depends on meeting the policy’s specified personal-history, tumor-feature, family-history, or predictive-model thresholds. Examples include meeting BRCA probability thresholds (Tyrer-Cuzick/BRCAPro/Penn11), PREMM5/MMRpro/MMRpredict thresholds for Lynch syndrome, specified family-history patterns (first-degree relatives with multiple primaries or relatives with Lynch-associated cancers), or tumor findings such as dMMR or tumor-detected P/LP variants. Known familial mutation testing or single-gene testing is considered medically necessary when a familial pathogenic variant is present.

For individuals without a personal history, coverage is contingent on family-history patterns or risk-score thresholds specified in the policy. The policy cites examples such as a Tyrer-Cuzick/BRCAPro/Penn11 score ≥ 5% for BRCA1/2 consideration and PREMM5/MMRpro/MMRpredict ≥ 5% for Lynch syndrome when no personal history exists; alternative lower thresholds (e.g., PREMM5 ≥ 2.5%) are allowed in some clinical contexts. Documentation of detailed family history is required to apply these criteria.

The policy includes adenomatous polyposis testing eligibility: testing is recommended for individuals with ≥ 20 cumulative adenomas, and may be considered for those with 10–19 adenomas or certain extraintestinal features. Family history of a known pathogenic variant in polyposis genes or certain phenotype features also meet testing criteria.

Personal-history–based coverage nodes require that the individual have a qualifying Primary Solid Tumor (excluding basal or squamous cell skin cancer) plus one or more specified features (for example, breast cancer diagnosed ≤50, metastatic breast cancer, triple-negative histology, Ashkenazi ancestry, male breast cancer, or tumor genomic findings with germline implications) to meet medical necessity for multigene panel testing.

When prior limited testing (e.g., negative BRCA1/2 by limited methods) exists but clinical criteria remain suggestive, the policy supports subsequent multigene panel testing for individuals who meet additional clinical criteria; studies demonstrate pathogenic variants in non-BRCA genes in such populations. Documentation of prior testing and rationale for further testing should be provided.

Lynch syndrome-related eligibility includes tumor dMMR findings, predictive-model thresholds (PREMM5/MMRpro/MMRpredict), and family-history patterns (first- or second-degree relatives with early-onset LS cancers or multiple relatives with LS-related cancers). The policy allows consideration of a PREMM5 threshold of ≥ 2.5% in certain contexts for individuals with a personal history of CRC or endometrial cancer.

Adenomatous polyposis eligibility emphasizes personal adenoma counts and specific associated features; a family history of a known pathogenic variant in polyposis genes qualifies an individual for testing, and tumor APC P/LP findings prompt germline consideration when other criteria are met.

The policy follows guideline-based tumor-specific recommendations: for pancreatic adenocarcinoma, NCCN recommends comprehensive germline testing for any confirmed pancreatic cancer; for prostate cancer and other tumor types, testing is indicated when NCCN or specialty society criteria are met. Genetic counseling and review of family history are part of the evaluation for tumor-specific testing.

When tumor genomic testing identifies pathogenic variants in genes with known germline implications, the policy indicates germline testing should be offered regardless of other eligibility criteria. Professional guidance (ASCO) supports offering germline testing when such tumor findings are present.

Known familial mutation testing and targeted single-gene testing (including BRCA1/2 founder-variant testing where appropriate) are considered proven and medically necessary when a familial pathogenic or likely pathogenic variant has been identified; prior negative limited testing may prompt additional panel testing if clinical criteria apply.

The policy requires documentation to support eligibility: a contemporary pedigree or detailed personal and family cancer history, ages at diagnosis, relationship degrees, tumor dMMR or tumor genomic findings, and predictive-model scores (e.g., PREMM5) should be included in records submitted with testing requests. Providers are encouraged to involve genetics specialists for complex cases.

Coverage decisions are tied to the specific criteria lists; testing outside the enumerated indications (for example, broad population screening or panels used for investigational polygenic risk scoring) are not supported. The policy reiterates that germline testing should be offered when it will inform patient management or family risk assessment and when criteria are met.

Eligibility for testing may be influenced by prior tumor or germline testing results; for example, tumor dMMR or tumor-detected P/LP variants warrant consideration of germline testing regardless of family history, and individuals previously negative for BRCA1/2 but meeting other criteria may be candidates for broader panel testing.

Provider Actions, Documentation, and Counseling

Note

Coding and Authorization Reference

Procedure and panel codes are provided for reference only. Listing a code does not imply coverage or payment. Verify member benefits and applicable laws; inclusion of a code is not a guarantee of reimbursement.

Use listed codes when requesting coverage but confirm member-specific benefits.
Providers should not assume coverage solely because a code appears in this policy.

Prior Authorization

Guideline-Based Indication for Testing

Offer genetic testing based on guideline-driven indications (ASCO/SSO, NCCN, ACOG, ACMG). Consider personal and family history, tumor findings, age at diagnosis, ancestry, and treatment implications when deciding to test for BRCA1/2 or ordering multigene panels.

ASCO/SSO: Offer BRCA1/2 testing for most newly diagnosed individuals ≤65 and for select older individuals when results affect management.
ACOG/ACMG/NCCN: Use established criteria such as early age at onset, triple-negative histology, Ashkenazi Jewish ancestry, or relatives with known P/LP variants.

Prior Authorization

Clinical-Criteria Driven Authorization

Coverage authorization is contingent on meeting the clinical criteria specified by guideline sources (NCCN, ASCO/SSO, Lynch and other syndrome-specific criteria). Testing requests should document how the individual meets applicable clinical criteria.

Testing is clinically indicated when NCCN or syndrome-specific criteria are met (e.g., known family P/LP variant, prior limited testing with ongoing clinical suspicion, tumor P/LP on somatic testing with germline implications).
Requests falling outside listed clinical criteria may not meet coverage.
Document the specific guideline(s) and criteria met when submitting for authorization.

Documentation Required

Specialist Involvement Recommended

When multigene panels include genes of uncertain or limited clinical utility, involve specialists with expertise in cancer risk assessment for ordering and interpretation to avoid inappropriate testing and mismanagement.

Genetic counselors or clinicians experienced in hereditary cancer syndromes are recommended for complex cases or large panels.
Specialist involvement is especially important when panels include low- or moderate-penetrance genes or genes lacking evidence to guide management.

Denial Risk

Use of Multigene Panels

Multigene panels should be targeted to the most likely syndrome based on personal and family history. Panels that indiscriminately include genes lacking evidence to support changes in management are discouraged.

Prefer targeted gene analysis when a single syndrome is most likely.
If multiple syndromes are on the differential, a phenotype-directed multigene panel may be appropriate.
Avoid large panels that include genes without clear clinical utility unless specialist input justifies inclusion.

Denial Risk

Criteria-Based Coverage Risk

Coverage risk increases when testing is requested outside established clinical criteria (e.g., Lynch syndrome criteria, NCCN indications) or without adequate documentation of family/tumor history.

Testing requests lacking documented criteria or pedigree information may be denied.
Provide clear justification tying the requested test to guideline-based indications to reduce denial risk.

Documentation Required

Required Family History Documentation

Document personal and family cancer history in the medical record using a pedigree drawing/diagram with standardized nomenclature. The pedigree should be contemporaneous and included with the testing request.

Include relationships, ages at diagnosis, cancer types, and ancestry where relevant.
Attach the pedigree to the authorization request and testing form.

Documentation Required

Analytic Requirements for Genetic Testing

Genetic testing should include full gene sequencing and deletion/duplication analysis (and detection of known P/LP variants where applicable) and must be performed in an appropriately accredited laboratory (CLIA-compliant).

Ensure tests include both sequencing and large rearrangement (duplication/deletion) analysis for genes where clinically relevant.
Use CLIA-certified labs; FDA clearance alone does not establish coverage.

Documentation Required

Required Clinical Documentation

Required clinical documentation for authorization includes a contemporaneous pedigree, detailed personal and family cancer history, indication tied to guideline criteria, and tumor testing results when relevant (e.g., dMMR, tumor P/LP findings).

If tumor genomic testing identified a P/LP variant, include those results and note clinical implications for germline testing.
Include PREMM5 or other predictive model scores when used for Lynch syndrome risk assessment.

Documentation Required

Documentation of Family History and Specialist Involvement

Testing and cancer risk assessment should document review of family history and note any specialist (genetic counselor or cancer genetics expert) involvement in ordering or interpretation, particularly for complex cases or panels including genes of uncertain utility.

Record the name and qualifications of the specialist who counseled or approved the test when applicable.
Document counseling about potential for VUS findings and that VUS should not drive clinical management.

Prior Authorization

Targeted Testing Before Broad Panels

Targeted gene testing is preferred when a single syndrome is most likely; multigene panels are appropriate when multiple syndromes are plausible or when prior limited testing was negative but clinical suspicion remains.

Individuals previously negative for BRCA1/2 who meet additional clinical criteria may be candidates for subsequent multigene panel testing.
Weigh risks of increased VUS detection and longer turnaround times with larger panels.

Note

Not Applicable

Not applicable.

Coding and Risk Thresholds

BRCA codesmixed

0138U	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) mRNA sequence analysis (List separately in addition to code for primary procedure).
81162	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) gene analysis; full sequence analysis and full duplication/deletion analysis (i.e., detection of large gene rearrangements).
81163	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) gene analysis; full sequence analysis.
81164	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) gene analysis; full duplication/deletion analysis (i.e., detection of large gene rearrangements).

Proprietary panel CPT/HCPCS (U-codes)mixed

0101U	Hereditary colon cancer disorders (e.g., Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (15 genes [sequencing and deletion/duplication], EPCAM and GREM1 [deletion/duplication only]).
0102U	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (17 genes [sequencing and deletion/duplication]).
0103U	Hereditary ovarian cancer (e.g., hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis panel utilizing a combination of NGS, Sanger, MLPA, and array CGH, with MRNA analytics to resolve variants of unknown significance when indicated (24 genes [sequencing and deletion/duplication], EPCAM [deletion/duplication only]).
0129U	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), genomic sequence analysis and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, and TP53).
0130U	Hereditary colon cancer disorders (e.g., Lynch syndrome, PTEN hamartoma syndrome, Cowden syndrome, familial adenomatosis polyposis), targeted mRNA sequence analysis panel (APC, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, and TP53) (List separately in addition to code for primary procedure).
0131U	Hereditary breast cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), targeted mRNA sequence analysis panel (13 genes) (List separately in addition to code for primary procedure).
0132U	Hereditary ovarian cancer-related disorders (e.g., hereditary breast cancer, hereditary ovarian cancer, hereditary endometrial cancer), targeted mRNA sequence analysis panel (17 genes) (List separately in addition to code for primary procedure).
0133U	Hereditary prostate cancer-related disorders, targeted mRNA sequence analysis panel (11 genes) (List separately in addition to code for primary procedure).
0134U	Hereditary pan cancer (e.g., hereditary breast and ovarian cancer, hereditary endometrial cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (18 genes) (List separately in addition to code for primary procedure).
0135U	Hereditary gynecological cancer (e.g., hereditary breast and ovarian cancer, hereditary endometrial cancer, hereditary colorectal cancer), targeted mRNA sequence analysis panel (12 genes) (List separately in addition to code for primary procedure).

1–10 of 15

1/2

Multi-gene panel CPT codesCPT

81432	Genomic sequence analysis panel, 5 or more genes (hereditary breast cancer-related disorders) - interrogation for sequence variants and copy number variants.
81435	Genomic sequence analysis panel, 5 or more genes (hereditary colon cancer-related disorders) - interrogation for sequence variants and copy number variants.
81437	Genomic sequence analysis panel, 5 or more genes (hereditary neuroendocrine tumor-related disorders) - interrogation for sequence variants and copy number variants.
81441	Inherited bone marrow failure syndromes sequence analysis panel, must include sequencing of at least 30 genes (includes listed genes such as BRCA2, BRIP1, PALB2, RAD51C, etc.).
81479	Unlisted molecular pathology procedure.

Risk score thresholds for BRCA1/2 — Tyrer-Cuzick, BRCAPro, Penn11

Personal history thresholdTyrer-Cuzick, BRCAPro, or Penn11 score ≥ 2.5% for individuals with a personal history of a primary solid tumor

No personal history thresholdTyrer-Cuzick, BRCAPro, or Penn11 score ≥ 5% for individuals with no personal history of a primary solid tumor

Context of useThese risk-model thresholds are referenced as part of criteria that trigger consideration of BRCA1/2 testing or multigene panel testing

Lynch syndrome prediction score thresholds — PREMM5, MMRpro, MMRpredict

Personal history thresholdPREMM5, MMRpro, or MMRpredict score ≥ 2.5% for individuals with a personal history (consider for Lynch evaluation)

No personal history thresholdPREMM5, MMRpro, or MMRpredict score ≥ 5% for individuals with no personal history

Model examplesPREMM5, MMRpro, and MMRpredict are the predictive models referenced for estimating MMR gene pathogenic variant probability

PREMM5 risk threshold

PREMM5 actionable threshold (personal history)Individuals with a personal history of colorectal and/or endometrial cancer: PREMM5 ≥ 2.5% should be considered for multigene panel testing (MGPT)

PREMM5 use without personal historyIndividuals without a personal history of CRC/EC may use PREMM5 ≥ 2.5% (rather than ≥5%) to select for MMR testing when applied with clinical judgment

Relation to other modelsPREMM5 thresholds are used alongside MMRpro/MMRpredict model thresholds referenced elsewhere in the policy

Adenoma count threshold

Recommended testing threshold≥ 20 cumulative adenomas: genetic testing for adenomatous polyposis is recommended

Consider testing range10–19 cumulative adenomas: genetic testing may be considered (clinical judgment may apply)

Other indicationsTesting also recommended for family history of a known pathogenic variant, CHRPE, cribriform‑morular papillary thyroid cancer, or family unwilling/unable to test

Definitions and Terminology

Close Blood Relatives — degree definitions

First‑degree relativesParents, siblings, and offspring

Second‑degree relativesHalf‑siblings, aunts/uncles, grandparents, grandchildren, nieces/nephews affected on same side of family

Third‑degree relativesFirst cousins, great‑aunts/uncles, great‑grandchildren, and great grandparents affected on same side of family

Multi‑Gene Panel — definition and scope

DefinitionMulti‑Gene Panel: genetic tests using next‑generation sequencing to test multiple genes simultaneously; for this policy a Multi‑Gene Panel consists of five or more genes

Typical contentPanels often include sequence analysis and large deletion/duplication analysis across multiple cancer predisposition genes

Use considerationsPanels may include low‑ or moderate‑risk genes that affect clinical utility and management decisions; gene selection should be guided by clinical context

Pathogenic / Likely Pathogenic (P/LP) variant — definition

DefinitionPathogenic/likely pathogenic (P/LP) variant: a genetic alteration classified as disease‑causing or likely disease‑causing

ImplicationIdentification of a P/LP variant indicates increased risk for associated hereditary cancer syndromes and may inform management and cascade testing

Testing standardsClassification follows established variant interpretation frameworks referenced in guideline context

Multigene hereditary cancer panel — definition

DefinitionMultigene hereditary cancer panel: a laboratory test that sequences multiple cancer predisposition genes and often includes large deletion/duplication analysis

Typical methodsAnalytic methods include NGS sequence analysis and targeted deletion/duplication assays (e.g., MLPA) as appropriate

Panel sizePolicy treats multigene panels as those including five or more genes; proprietary and CPT panel codes are listed as references

Lynch syndrome — definition

DefinitionLynch syndrome: used only when germline heterozygous P/LP variants are identified in MMR genes MLH1, MSH2, MSH6, PMS2 or 3′ terminal deletions of EPCAM

Clinical contextLS identification guides colorectal and endometrial cancer surveillance and family cascade testing

Testing triggersLS is evaluated when tumor dMMR, predictive model thresholds, or specified family history patterns are present

HBOC multigene panels — typical genes included

Core genes commonly includedHBOC multigene panels typically include ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, STK11, TP53

PurposePanels are comprised of clinically validated hereditary breast and ovarian cancer genes to inform risk estimates and management

Expert counselingComprehensive genetic counseling is emphasized when multigene panels include genes beyond BRCA1/2 due to variable penetrance and utility

dMMR — definition

DefinitiondMMR: deficient mismatch repair in a tumor as determined by PCR, NGS, or immunohistochemistry (IHC)

Clinical significanceTumor dMMR (MSI‑high or absent MMR protein expression) is a trigger for Lynch syndrome evaluation and germline testing

PREMM5 — definition

DefinitionPREMM5: a predictive model (PREdiction Model for gene Mutations) estimating cumulative probability of MLH1, MSH2, MSH6, PMS2, and EPCAM gene mutations related to Lynch syndrome

RolePREMM5 is used with threshold percentages (e.g., ≥2.5% or ≥5%) to identify individuals for MMR gene testing

Germline testing — definition and implications

DefinitionGermline testing: genetic testing to identify inherited pathogenic variants that may have implications for patient management and family members

ImplicationsDetecting germline P/LP variants can inform surveillance, preventive measures, treatment decisions, and cascade testing of relatives

RNA testing concurrent with DNA — definition and intended use

DefinitionConcurrent RNA testing with DNA: RNA‑based assays performed alongside DNA testing to clarify splicing and aid variant interpretation

Policy stancePolicy states insufficient evidence to support routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels

Intended useUsed to clarify potential splice‑affecting variants identified on DNA testing, but broader clinical utility remains unproven

Ordering, Counseling, and Specialist Involvement (Supplement)

Documentation Required

Provide pre-test genetic counseling before germline testing

Pre-test genetic counseling is strongly recommended to inform individuals about the advantages, limitations, and potential outcomes of testing and to facilitate informed consent.

NSGC and ASCO recommend counseling to review personal and family history, discuss risks/benefits/limitations, and assist with informed consent.
Counseling should cover potential for VUS findings and implications for family cascade testing.

Documentation Required

Repeat pre-test counseling as needed and document

Repeat and reinforce pre-test counseling as needed to ensure the patient understands the implications of testing, limitations, and potential outcomes.

NSGC practice resources emphasize comprehensive education, psychosocial assessment, and informed consent processes.
Document repeated counseling encounters in the medical record when applicable.

Documentation Required

Address benefits, limitations, and likelihood of results during counseling

Ensure counseling addresses the advantages and limitations of testing for the specific individual, including the likelihood of identifying mutations and the possibility of uncertain results.

NSGC recommends discussing the likelihood of identifying a mutation and potential psychosocial and management implications.
Tailor counseling to the individual's cancer type, family history, and planned panel composition.

Documentation Required

Document counseling and informed consent prior to testing

Document that pre-test counseling was offered or provided and that the patient gave informed consent prior to ordering genetic testing.

ASCO/SSO and NSGC highlight the importance of informed consent and documentation of counseling steps.
Include counseling notes, educational materials discussed, and patient's understanding in the record.

Documentation Required

Take and record a comprehensive family history before testing

Obtain a comprehensive family history prior to testing; ASCO recommends a thorough family-history assessment as part of offering germline testing.

Record first- and second-degree relatives, ages at diagnosis, tumor types, and multiple primary cancers to apply policy criteria.
A contemporaneous pedigree drawing/diagram should be included with testing requests.

Documentation Required

Emphasize counseling before multigene panels due to VUS risk

Reinforce pre-test counseling for patients considering multigene panels given the higher probability of uncertain findings and the potential need for specialist interpretation.

NSGC resources stress counseling for complex panels and managing psychosocial impacts of results.
Document counseling that specifically addressed panel scope and VUS risk.

Documentation Required

Provide additional counseling for complex or uncertain cases

Provide repeated counseling when indicated (e.g., complex family histories, prior testing, or when test results are uncertain) and document these sessions.

NSGC recommends ongoing education, discussion of management options, and dissemination planning for family implications.
Record follow-up counseling and any decisions about cascade testing.

Documentation Required

Have ordering guided by genetic counseling and genetics specialists

Ensure ordering is guided by genetic counseling and specialists when possible; involve genetic counselors or experienced providers in test selection and interpretation.

Ordering clinicians should engage genetics expertise to choose appropriate panels and mitigate harms from uncertain results.
Document that counseling/consultation informed the ordering decision.

Documentation Required

Use providers trained in hereditary cancer evaluation for testing

Testing and evaluation should be performed by providers familiar with hereditary cancer diagnosis and management (e.g., genetic counselors, clinical geneticists, or oncology providers with genetics expertise).

ASCO and NSGC guidance recommend that health care providers conducting genetic evaluations be knowledgeable about hereditary cancer management.
Involve specialists when panel interpretation or management decisions are complex.

Documentation Required

Document that genetic counseling guided the test order

Ensure ordering is informed by genetic counseling and specialist input; document that counseling informed test choice and that potential harms of uncertain results were discussed.

ASCO/SSO recommend individualized consultation for test selection and interpretation.
Document the counseling content that guided ordering decisions.

Documentation Required

Ordering clinician must ensure documentation and informed consent

The ordering clinician should ensure appropriate documentation (family history, counseling, informed consent) and be prepared to manage results; genetics providers and oncologists commonly perform ordering.

ASCO guidance notes that genetics providers and oncologists most commonly order testing but the ordering clinician remains responsible for documentation and informed consent.
Ensure a plan is documented for result disclosure and cascade testing if a P/LP variant is identified.

Documentation Required

Involve expert providers for panels with uncertain-utility genes and document involvement

For panels that include genes of uncertain utility, involve providers with expertise in cancer risk assessment for ordering and interpretation and document their role.

ASCO provisional opinion recommends specialized involvement for MGPTs that include uncertain-utility genes.
Record specialist consultation to support the decision to include such genes on a panel.

Tests and Uses Not Covered

The policy states that not covered items include multi-gene hereditary cancer panels when used for indications not specified in the criteria, concurrent RNA panel testing with BRCA1/2 or multigene panels, and tests or panels that include genes without demonstrated clinical validity or actionability. Additionally, genetic tests used solely for polygenic risk scoring are considered unproven and not medically necessary.

Tests or panels that include genes without established clinical validity or actionability are discouraged and may be considered not covered when used to direct management in the absence of guideline-based indications. The policy requires that testing be performed in appropriately accredited laboratories and that test selection be guided by clinical relevance.

Multi-gene hereditary cancer panels performed for indications not included in the policy criteria are considered not covered. The policy also cites limited evidence for multisyndrome panels to improve clinical outcomes and flags concerns about panels used without clear clinical purpose.

The policy references a 2023 Hayes review and other literature noting minimal or unclear support for using comprehensive multisyndrome panels to guide patient management; where multisyndrome panels are used, the policy favors targeted testing guided by specialist input and documentation of clinical rationale.

Routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels is described as unsupported by sufficient evidence for broad coverage and is therefore generally not covered for routine use. Limited studies suggest RNA testing can increase diagnostic yield in select cases but are insufficient to justify routine concurrent use.

OpenPayer

Genetic Testing for Hereditary Cancer

Coverage Criteria for Hereditary Cancer Testing

Specific Covered Indications and Syndrome-based Testing

Eligibility Requirements and Known-Familial Mutation Testing

Provider Actions, Documentation, and Counseling

Coding and Risk Thresholds

Definitions and Terminology

Ordering, Counseling, and Specialist Involvement (Supplement)

Tests and Uses Not Covered

Background and Evidence Summary

Additional Definitions and Terms