CurrentUnitedHealthcarePolicy CS049.Z

Genetic Testing for Hereditary Cancer

Defines coverage criteria for single-gene and multi-gene hereditary cancer genetic testing (including BRCA1/2 and multi-gene panels), applicable exclusions (RNA panels, polygenic risk scoring), documentation requirements, applicable CPT/HCPCS molecular codes, and state-specific applicability.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer

Policy CodePolicy CS049.Z

Change TypeRevised (material) — multiple coverage criteria edits; additions and clarifications

Effective DateJune 1, 2025

Next Review DateN/A

Key ActionSubmit contemporaneous medical records including a pedigree drawing/diagram to document personal and family history when requesting testing.

POLICY UPDATE CHANGES

Policy revised 06/01/2025 with multiple coverage criteria edits and clarifications for personal and family history indications.

Added language that this Medical Policy does not apply to Idaho and Kansas; refer to state-specific versions.

Added Unproven/Not Medically Necessary statement that polygenic risk scoring for hereditary cancers is unproven and not medically necessary.

Added CPT code 0495U to Applicable Codes.

Updated definitions for High Penetrance Breast Cancer Susceptibility Genes and Limited Family History.

Supporting Information sections (Description of Services, Clinical Evidence, FDA, References) updated to current information; archived previous policy version CS049.Y.

BRCA1/2 + MGPTCovered Indications

Coverage Summary

This policy (CS049.Z) covers clinical criteria for single-gene and multigene hereditary cancer genetic testing, including BRCA1/2 and multigene panels, and specifies documentation and coding requirements. Status: CURRENT. Effective date: June 1, 2025. The policy excludes applicability to certain states; specifically, Idaho and Kansas (see state-specific versions).

High-level policy data

policy_numberCS049.Z

effective_date2025-06-01

scope_summaryDefines coverage criteria for single-gene and multigene hereditary cancer testing, exclusions (RNA panels, PRS), documentation requirements, CPT/HCPCS codes, and state-specific applicability.

coverage_stancemixed (BRCA1/2 and syndrome-directed MGPT covered for specified indications; RNA panels and polygenic risk scoring not medically necessary)

primary_covered_indicationsBRCA1/2 testing for eligible individuals (e.g., breast cancer ≤65 yrs) and multigene panels for BRCA-related and other syndrome-specific indications (e.g., HBOC, LS, MGPT when criteria met). Primary covered genes highlighted: BRCA1, BRCA2, and multigene panels (MGPT).

Medical-Necessity Criteria

General principles

Pre-test genetic counseling is strongly recommended to inform individuals about the potential benefits, limitations, and implications of testing. Single-gene testing and testing for a known familial pathogenic/likely pathogenic (P/LP) variant are proven and medically necessary when consistent with the criteria below.

General principles

- Pre-test genetic counseling is strongly recommended.

- Single-gene testing and known familial mutation testing is proven and medically necessary.

BRCA1/2 testing - individuals with personal history of breast cancer

BRCA1/2 testing is proven and medically necessary for individuals with a personal history of breast cancer when ALL of the following are met:

BRCA1/2 testing - individuals with personal history of breast cancer

Coding

Referenced molecular/procedure codes (informational)mixed

0138U	BRCA1 and BRCA2 mRNA sequence analysis (list separately in addition to code for primary procedure)
0101U	Hereditary colon cancer disorders genomic sequence analysis panel (15 genes)
0102U	Hereditary breast cancer-related disorders genomic sequence analysis panel (17 genes)
0103U	Hereditary ovarian cancer genomic sequence analysis panel (24 genes) (truncated description)
0129U	Hereditary breast cancer-related disorders genomic sequence and deletion/duplication panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, TP53)
0130U	Hereditary colon cancer disorders targeted mRNA sequence analysis panel (list separately)
0131U	Hereditary breast cancer-related targeted mRNA sequence analysis panel (13 genes) (list separately)
0132U	Hereditary ovarian cancer-related targeted mRNA sequence analysis panel (17 genes) (list separately)
0133U	Hereditary prostate cancer-related targeted mRNA sequence analysis panel (11 genes) (list separately)
0134U	Hereditary pan cancer targeted mRNA sequence analysis panel (18 genes) (list separately)

1–10 of 24

1/3

Recommended minimum genes for germline MGPT (by syndrome per NCCN/CGA-IGC/others)mixed

genes	Breast/HBOC: BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, TP53, ATM, BARD1, BRIP1, CHEK2
genes	Ovarian: ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2, RAD51C, RAD51D
genes	CRC/LS: APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM, BMPR1A, SMAD4, PTEN, STK11, TP53, POLD1, POLE, AXIN2, GREM1, NTHL1, POLE, POLD1, MSH3
genes	Pancreatic: ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, EPCAM, PALB2, STK11, TP53
genes	Prostate: ATM, BRCA1, BRCA2, CHEK2, HOXB13, TP53

Genes / gene lists referenced for testing (by indication)mixed

BRCA1	Breast/ovarian cancer gene
BRCA2	Breast/ovarian cancer gene
PALB2	Breast cancer gene
CDH1	Hereditary diffuse gastric cancer / breast cancer gene
PTEN	Cowden syndrome gene
STK11	Peutz-Jeghers syndrome gene
TP53	Li-Fraumeni syndrome gene
ATM	Various cancers, recommended in some panels
BARD1	Breast cancer gene
CHEK2	Breast/colon/prostate cancer gene

1–10 of 48

1/5

FDA / Regulatory notesmixed

CLIA	Laboratories performing genetic tests are regulated under CLIA

Added/Applicable CPTCPT

0495U

CPT code added to Applicable Codes list (description not provided in this part)

Provider Actions & Prior Authorization

Prior Authorization

Medical necessity based on criteria

Coverage for genetic testing is determined by whether the individual meets the clinical criteria in this policy. Prior authorization may be required and medical records (including pedigree/family history, clinical notes, and test reports) may be requested to verify that medical necessity criteria are met. Submission of records does not guarantee coverage; applicable federal, state, and contractual rules apply.

Medical records may be requested to confirm criteria are met
Prior authorization required when indicated by payer rules
Meeting clinical criteria is required for coverage

Documentation Required

Pedigree / family history documentation

Provide a pedigree diagram using standardized genetic nomenclature and include detailed personal and family history (relationship, age at diagnosis, cancer type, and ancestry). Include contemporaneous medical records with the testing request (e.g., request form) to support clinical indications.

Background & Evidence

Hereditary cancer genetic testing is performed to identify individuals at increased lifetime risk of cancer and to inform diagnosis, prognosis, treatment, and cascade testing of relatives; an estimated 5-10% of cancers are hereditary. BRCA1/2 are high-penetrance genes: lifetime breast cancer risk for women with BRCA1 P/LP variants is ~60-72% and for BRCA2 ~55-69%, with substantially increased ovarian cancer risks as well. Other genes (e.g., CDH1, PALB2, PTEN, STK11, TP53, ATM, BRIP1) are also associated with elevated risks for breast, ovarian, pancreatic, colorectal, prostate and other cancers, with variable penetrance across genes.

Multigene panels (MGPT) can be efficient and may increase identification of pathogenic/likely pathogenic (P/LP) variants across syndromes and influence management and treatment decisions. However, broader panels commonly include low- or moderate-penetrance genes and genes with limited or evolving evidence linking them to cancer risk; this increases the likelihood of variants of uncertain significance (VUS) and may produce results that lack clear management pathways. Therefore panel selection should be guided by phenotype, age at presentation, and detailed personal and family history, and results should be interpreted with genetics expertise.

A thorough, contemporaneous pedigree-based family history (first-, second-, and third-degree relatives; ages at diagnosis; tumor types; bilateral disease; and relevant non-cancer features) is emphasized as essential prior to testing. Validated risk assessment tools (for example, Tyrer-Cuzick/BRCAPro/BOADICEA/PREMM/MRpro) are recommended to estimate prior probabilities and inform whether testing meets policy thresholds and clinical indications.

Key evidence and prevalence findings

Estimated hereditary cancer proportion

Definitions

Term	Definition
Age Guidelines
For the statements that include Age Guidelines, a person is considered to be 45 years of age up until the day before their 46th birthday, and a person is considered to be 50 years of age up until the day before their 51st birthday.
BRCA-Related Cancers
Breast Cancer, Ovarian Cancer/fallopian tube cancer/primary peritoneal cancer, pancreatic cancer, or prostate cancer.
Close Blood Relatives
First-degree: parents, siblings, offspring; Second-degree: half-siblings, aunts/uncles, grandparents, grandchildren, nieces/nephews affected on same side; Third-degree: first cousins, great-aunts/uncles, great-grandchildren, great grandparents affected on same side.
Limited Family History
Fewer than two known first-degree or second-degree female relatives surviving beyond 45 years of age on either or both sides of the family (e.g., adopted).
Multi-Gene Panel
Genetic tests that use next-generation sequencing to test multiple genes simultaneously; for this policy, consists of five or more genes.
Primary Solid Tumor
An abnormal mass of tissue, typically not containing cysts or liquid component, which is the original/first tumor in the body; excludes basal or squamous cell skin cancer per policy.
P/LP
Pathogenic or likely pathogenic variant.
VUS
Variant of uncertain significance — not clinically actionable and should not change management.
dMMR
Deficient mismatch repair identified by MSI-high or abnormal MMR immunohistochemistry (IHC).
MGPT
Multigene panel testing (germline) using next-generation sequencing.
PRS
Polygenic risk score — aggregate risk estimate from multiple genetic variants.
High Penetrance Breast Cancer Susceptibility Genes (updated)
Genes in which certain mutations are related to significantly increased likelihood of Breast Cancer; examples include BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53 (NCCN v1.2025).
Limited Family History (updated)
Fewer than two known first-degree or second-degree female relatives surviving beyond 45 years of age on either or both sides of the family (e.g., individual who is adopted) (NCCN).

Revision History

2025-06-01material_revisionLatest

Policy revised with multiple coverage criteria edits and clarifications for personal and family history indications, including wording changes (e.g., 'Primary Solid Tumor(s)'), addition of malignant phyllodes tumor, updated male-related breast cancer language to 'assigned male at birth', expanded tumor tissue pathogenic variant language with example genes, and added family-history criteria including triple-negative breast cancer and male relative with breast cancer.

2025-06-01added_state_exclusionLatest

Added language that this Medical Policy does not apply to the states of Idaho and Kansas; refer to state-specific policy versions.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer

Policy CodePolicy CS049.Z

Change TypeRevised (material) — multiple coverage criteria edits; additions and clarifications

Effective DateJune 1, 2025

Next Review DateN/A

Key ActionSubmit contemporaneous medical records including a pedigree drawing/diagram to document personal and family history when requesting testing.

On This Page

Multi-Gene hereditary cancer panel - individuals with a personal history of a Primary Solid Tumor

Multi-gene hereditary cancer panel testing is proven and medically necessary for individuals with a personal history of a Primary Solid Tumor (excluding basal or squamous cell skin cancer) when ONE of the following personal-history criteria is met:

Multi-Gene hereditary cancer panel - individuals with a personal history of a Primary Solid Tumor

- Breast cancer diagnosed at age 50 or younger.

- Metastatic breast cancer.

- Multiple primary breast cancers (including bilateral primaries).

- Triple-negative breast cancer.

- Lobular breast cancer with personal or family history of diffuse gastric cancer.

- Breast cancer with Ashkenazi Jewish ancestry.

- Breast cancer in an individual assigned male at birth.

- Breast cancer with unknown or limited family history.

- Breast cancer or prostate cancer with at least one first- or second-degree relative with a BRCA-related cancer.

- Ovarian cancer (including fallopian tube and primary peritoneal).

- Pancreatic cancer.

- Metastatic prostate cancer.

- Cancer associated with Lynch syndrome.

- Neuroendocrine tumors (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma).

- Malignant phyllodes tumors.

- At least two different primary solid tumors (excluding basal/squamous cell skin cancer).

Multi-Gene hereditary cancer panel - personal history plus family history

Multi-gene hereditary cancer panel testing is proven and medically necessary for individuals with a personal history of a Primary Solid Tumor (excluding basal or squamous cell skin cancer) when the personal tumor history PLUS any of the following family-history criteria are present:

Multi-Gene hereditary cancer panel - personal history plus family history

- At least one close blood relative with a cancer associated with Lynch syndrome.

- At least one close blood relative diagnosed with a primary solid tumor at age 40 or younger.

- At least two close blood relatives (in addition to the affected individual) on the same side of the family diagnosed with any primary solid tumor (excluding basal/squamous cell skin cancer).

Multi-Gene hereditary cancer panel - personal history with tumor tissue findings or risk models

Multi-gene hereditary cancer panel testing is proven and medically necessary for individuals with a personal history of a Primary Solid Tumor when ANY of the following tumor tissue findings or validated risk-model thresholds are met:

Multi-Gene hereditary cancer panel - personal history with tumor tissue findings or risk models

- A pathogenic variant was detected in tumor tissue that has clinical implications if present in the germline (examples: BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C, RAD51D, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC2, VHL, APC, PTEN, RB1, TP53).

- Tumor testing demonstrating microsatellite instability–high (MSI-high) or immunohistochemistry (IHC) showing absence of one or more mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).

- Tyrer-Cuzick, BRCAPRO, or Penn II score ≥ 2.5% for a BRCA1/2 pathogenic variant.

- PREMM5, MMRpro, or MMRpredict score ≥ 2.5% for a Lynch syndrome gene mutation.

Genetic testing - individuals without personal history of a Primary Solid Tumor

Genetic testing (MGPT or targeted BRCA1/2 testing) is proven and medically necessary for individuals without a personal history of a Primary Solid Tumor when family-history criteria meet the thresholds below. The family-history rules include nested criteria and multiple combinatorial branches.

Genetic testing - individuals without personal history of a Primary Solid Tumor

- ONE of the following family-pattern criteria:

-- At least one first-degree relative with either:

--- Two or more different primary solid tumors (excluding basal/squamous cell skin cancer).

--- A cancer associated with Lynch syndrome.

--- A neuroendocrine tumor (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma).

-- At least one first- or second-degree relative with any of:

--- Breast cancer diagnosed at age 50 or younger.

--- Triple-negative breast cancer.

--- Breast cancer in a relative assigned male at birth.

--- Metastatic prostate cancer.

--- Ovarian cancer (including fallopian tube/primary peritoneal).

--- Pancreatic cancer.

-- At least one second-degree relative with either:

--- Two or more Lynch-syndrome–associated cancers.

--- Lynch-syndrome–associated cancer diagnosed at age 50 or younger.

-- Family history meeting any of the following broader patterns:

--- Two or more second-degree relatives on the same side with a cancer associated with Lynch syndrome.

--- At least three close blood relatives on the same side diagnosed with any primary solid tumor (excluding basal/squamous cell skin cancer).

--- Ashkenazi Jewish ancestry plus at least one close blood relative with a BRCA-related cancer.

--- A family member who meets diagnostic criteria for polyposis (personal history of ≥10 cumulative adenomas) and the affected relative is unwilling or unable to have genetic testing.

Not medically necessary / Unproven

The following uses of MGPT, RNA panel testing, and polygenic risk scoring are considered not medically necessary or unproven.

Not medically necessary / Unproven

- Multi-gene hereditary cancer panels for indications other than those specified above are unproven and not medically necessary.

- RNA panel testing for hereditary cancers (concurrent with or independent of DNA/MGPT) is unproven and not medically necessary for all indications.

- Genetic testing for the purpose of polygenic risk scoring (PRS) for hereditary cancers is unproven and not medically necessary for all indications.

General testing indications (per NCCN and other societies)

Per NCCN and selected society recommendations, multigene testing is indicated when it would inform diagnosis, prognosis, treatment, or cascade testing; specific indications include the following (ANY):

General testing indications (per NCCN and other societies)

- Known familial P/LP variant in a gene associated with hereditary cancer (confirmatory/targeted testing).

- Prior limited single-gene or panel testing that did not include genes now relevant to the individual/family.

- A pathogenic or likely pathogenic variant identified in tumor tissue that has potential germline relevance.

- Test results that would change systemic therapy, surgical management, or eligibility for targeted therapy (e.g., PARP inhibitors for BRCA1/2, immunotherapy for dMMR/MSI-high tumors).

- Patients meeting established syndrome-specific diagnostic criteria (e.g., clinical criteria for Li-Fraumeni, Cowden, hereditary diffuse gastric cancer, familial adenomatous polyposis, Lynch syndrome).

- Individuals with ancestry or family history that increases pre-test probability per guideline-based thresholds.

Breast cancer-specific indications

Breast cancer–specific testing recommendations (selected) — include both personal history and unaffected relative pathways. Use of MGPT is appropriate when ALL or ANY of the following apply.

Breast cancer-specific indications

- ALL: Personal history criteria (ONE of):

-- Breast cancer diagnosed at age ≤50 years.

-- Metastatic breast cancer.

-- Multiple primary breast cancers or bilateral primaries.

-- Triple-negative breast cancer diagnosed ≤60 years (or per guideline variant thresholds).

-- Lobular breast cancer with personal/family history of diffuse gastric cancer.

-- Breast cancer plus Ashkenazi Jewish ancestry.

-- Male breast cancer.

-- Breast cancer with limited or unknown family history.

-- Breast or prostate cancer with at least one first- or second-degree relative with a BRCA-related cancer.

- UNAFFECTED or relative-based criteria (ONE of):

-- At least one first-degree relative with two or more different primary solid tumors.

-- At least one first- or second-degree relative with breast cancer ≤50, triple-negative breast cancer, male breast cancer, metastatic prostate cancer, ovarian cancer, or pancreatic cancer.

-- Ashkenazi Jewish ancestry plus a close relative with a BRCA-related cancer.

- MAY BE CONSIDERED:

-- Individuals with a personal history of breast cancer diagnosed at ages 51–65 who do not otherwise meet higher-risk criteria.

- LOW PROBABILITY / NOT ROUTINELY RECOMMENDED:

-- Individuals with very limited family history and no other risk features; consider testing only if other clinical factors raise pre-test probability.

Ovarian cancer-specific indications

Ovarian cancer–specific indications — testing is indicated when ANY of the following are present:

Ovarian cancer-specific indications

- Personal history of ovarian, fallopian tube, or primary peritoneal cancer.

- Close blood relative with ovarian, fallopian tube, or primary peritoneal cancer.

- An estimated probability of ≥5% for a BRCA1/2 pathogenic variant by validated models (e.g., Tyrer-Cuzick, BRCAPRO, Penn II).

Prostate cancer-specific indications

Prostate cancer–specific indications — testing is indicated for select clinical and family-history patterns:

Prostate cancer-specific indications

- Metastatic prostate cancer or high-risk/very-high–risk localized disease (consider per guideline).

- Family history patterns of hereditary prostate or BRCA-related cancers (e.g., close relatives with early-onset breast, ovarian, pancreatic cancer or multiple affected relatives).

- MAY BE CONSIDERED: Germline testing in localized prostate cancer without high-risk features when family history or ancestry raises pre-test probability.

Lynch Syndrome (LS) testing criteria

Lynch syndrome (LS) testing criteria — include personal history, family patterns, tumor testing, and validated-model thresholds.

Lynch Syndrome (LS) testing criteria

- Personal history of colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, small intestinal, biliary tract, brain (glioblastoma), or sebaceous skin tumors consistent with Lynch-associated cancers.

- Family patterns meeting criteria (e.g., multiple affected relatives, early-onset cancers) or first-/second-degree relative with LS-associated cancer.

- Tumor testing showing deficient mismatch repair (dMMR) by IHC or MSI-high.

- PREMM5, MMRpro, or MMRpredict score ≥ 2.5% (consider higher threshold ≥5% for some unaffected-individual pathways).

- MAY BE CONSIDERED: Testing for individuals with suggestive but non-diagnostic family histories or borderline model scores.

Hamartomatous polyposis and related syndromes (USMSTF)

Hamartomatous polyposis and related syndromes (selected USMSTF triggers) — recommend genetic evaluation/genetic testing when any of the following are present:

Hamartomatous polyposis and related syndromes (USMSTF)

- Multiple hamartomatous polyps or syndromic features suggestive of juvenile polyposis, Peutz-Jeghers, or PTEN hamartoma tumor syndrome.

- Early-onset gastrointestinal polyps or family history consistent with these syndromes.

- Extraintestinal features consistent with syndrome-specific criteria.

ASCO recommendations for offering germline multigene panel testing

ASCO recommendations for offering germline multigene panel testing (selected guidance):

ASCO recommendations for offering germline multigene panel testing

- Offer MGPT when results would inform treatment, surveillance, or cascade testing, and when panels include genes with well-characterized cancer risks and clinical management guidelines.

- Consider inclusion of high- and moderate-penetrance genes relevant to the presenting cancer; avoid very large panels that include genes without established management guidance unless specific rationale documented.

- Tumor-testing–triggered germline evaluation: when a tumor harbors a P/LP variant with potential germline relevance, or when tumor testing demonstrates dMMR/MSI-high, offer germline testing that includes the relevant genes (e.g., MMR genes, BRCA1/2) to evaluate for hereditary etiology.

Individuals With a Personal History of a Primary Solid Tumor

Individuals with a personal history of a primary solid tumor (alternate wording — consistent with above) — testing is indicated when personal-history examples and tumor findings align with the criteria below:

Individuals With a Personal History of a Primary Solid Tumor

- Examples of qualifying personal-history features include breast, ovarian, pancreatic, metastatic prostate, neuroendocrine, malignant phyllodes tumors, multiple primaries, and early-onset cancers as listed elsewhere in this policy.

- A pathogenic variant identified in tumor tissue that has clinical implications if present in the germline meets criteria for germline testing.

Individuals With No Personal History of a Primary Solid Tumor

Individuals with no personal history of a primary solid tumor (updated family-history language) — testing criteria include family patterns and specific relative findings:

Individuals With No Personal History of a Primary Solid Tumor

- Family-history criteria include (but are not limited to) first- or second-degree relatives with early-onset breast cancer, triple-negative breast cancer, male breast cancer in a relative, ovarian cancer in a relative, pancreatic cancer in a relative, Lynch-syndrome–associated cancers in relatives, or Ashkenazi Jewish ancestry with a relative affected by BRCA-related cancer.

- Consider validated model thresholds (e.g., ≥5% for BRCA by Tyrer-Cuzick/BRCAPRO/Penn II) in appropriate unaffected individuals to guide testing decisions.

Unproven/Not Medically Necessary

Unproven/Not Medically Necessary (aligned with other not-medically-necessary sections):

Unproven/Not Medically Necessary

- Polygenic risk score (PRS) testing for hereditary cancer risk is unproven and not medically necessary.

- RNA-only panels (splicing or transcriptome panels) for hereditary cancer testing are unproven and not medically necessary when used alone; RNA testing concurrent with DNA/MGPT is also unproven and not medically necessary for all indications.

- MGPT for indications not specified in this policy is unproven and not medically necessary.

Documentation Required

Genetic counseling recommended

Document that pre-test and post-test genetic counseling occurred, and that informed consent addressing benefits, limitations, and potential implications was obtained. If counseling was not provided, include rationale and documentation of patient understanding.

Document pre- and post-test counseling in the medical record
Document informed consent specific to the genetic test

Documentation Required

Use validated risk models

When using quantitative risk thresholds, document which validated risk model was used and the calculated score. Acceptable models include Tyrer-Cuzick, BRCAPro, Penn11 for BRCA1/2 risk and PREMM5, MMRpro, MMRpredict for Lynch syndrome risk.

Record the risk model name and the patient’s score (e.g., Tyrer‑Cuzick = 5.2%)
Use validated models when applying policy thresholds

Prior Authorization

Panel selection & laboratory standards

When requesting multi-gene panels or BRCA1/2 testing, document the clinical rationale for panel selection (genes included and clinical relevance). Panels should include sequencing and deletion/duplication analysis when clinically indicated. Provide laboratory methodology and evidence of meeting quality standards.

Provide rationale for panel selection and list of genes included
Panels should include sequencing and del/dup testing where indicated
Include lab methodology and quality/validation information

Documentation Required

Offer germline testing when tumor testing reveals pathogenic variants

Offer germline multi-gene panel testing when tumor testing identifies a pathogenic or likely pathogenic variant that has potential germline implications. Examples of genes where germline follow-up is commonly indicated include BRCA1, BRCA2, MLH1, MSH2, MSH6, and PMS2.

Recommend germline MGPT when tumor testing reveals pathogenic/likely pathogenic variants
Examples: BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2

Denial Risk

RNA panel concurrent testing not routinely supported

Concurrent RNA panel testing is not routinely supported and may be denied absent strong clinical justification. If requesting concurrent RNA testing, provide clear rationale and supporting documentation that RNA analysis is necessary for interpretation or management.

Concurrent RNA testing may be denied without strong supporting rationale
Provide documentation linking RNA testing to clinical management

Documentation Required

Medical records may be required

Documentation submitted for prior authorization or review does not guarantee coverage. Coverage decisions remain subject to the member’s benefit plan, federal/state laws, and contract terms. Ensure state-specific exceptions are followed where applicable.

Submission of records does not guarantee payment
Coverage determined by benefit plan, contracts, and applicable law

Billing Rule

State-specific policy applicability

This policy does not apply to Idaho and Kansas. For members in those states, refer to the state-specific Genetic Testing for Hereditary Cancer policy versions noted in the Application section.

Policy not applicable in Idaho and Kansas — use state-specific versions

Concurrent RNA panel testing with DNA-based BRCA1/2 or multigene panels is not supported by sufficient high-quality evidence for routine use. Existing studies are limited and heterogeneous; while select reports show RNA testing can clarify splicing variants and may increase diagnostic yield in some cases (examples report relative increases), further high-quality studies and standards for interpretation are needed before routine concurrent RNA panels are recommended.

Evidence for clinical implementation of polygenic risk scores (PRS) for hereditary cancer risk assessment is currently insufficient. PRS performance varies by ancestry and improves when combined with clinical and non-genetic factors, but limitations in derivation populations, prediction accuracy, and clinical utility remain. Professional guidance (ACMG) cautions against routine clinical implementation of PRS unless providers and patients understand their limitations and how results would meaningfully guide evidence-based management.