ModifiedUnitedHealthcarePolicy CS049PA.W

Genetic Testing for Hereditary Cancer (for Pennsylvania Only)

This policy governs coverage criteria for genetic and molecular testing related to hereditary cancer for UnitedHealthcare members in Pennsylvania, including BRCA1/2 testing, multigene hereditary cancer panels, and exclusions for RNA panels, PRS, and WES/WGS.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer (for Pennsylvania Only)

Policy CodePolicy CS049PA.W

Change TypeCriteria and coding revisions

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionDocument clinical indication, family history, and pedigree when requesting multigene hereditary cancer testing; prior authorization may be required for listed codes.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria for multigene hereditary cancer panels for individuals with a personal history of a primary solid tumor, adding specific renal cell carcinoma-related criteria and serous tubal intraepithelial carcinoma.

Replaced Tyrer-Cuzick, BRCAPRO, or PENN11 score references with Tyrer-Cuzick, BRCAPRO, or CanRisk at both 2.5% and 5% BRCA1/2 probability cutoffs.

Whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes is unproven and not medically necessary.

Removed certain CPT codes for multigene panel reporting and added a set of CPT codes for whole exome/genome sequencing and related tests.

Updated medical records documentation section to require legible, complete documentation supporting medical necessity and noting that documentation may be required but does not guarantee coverage.

05/01/2026Policy effective

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

WES/WGSUnproven tests

PennsylvaniaApplies to

CPT addedWES/WGS codes added

Coverage Criteria for Hereditary Cancer Genetic Testing

Individuals with a personal history of a Primary Solid Tumor — BRCA1/2

Covered when ALL of the following are met

BRCA1/2 for breast cancer: Individual has personal history of breast cancer diagnosed at age 65 years or youngerage <=65

BRCA1/2 testing proven and medically necessary for this group

Individuals with a personal history of a Primary Solid Tumor — Multi-Gene Panel indications

Multi-Gene hereditary cancer Panel is covered when ANY one of the listed personal history criteria is met

Personal history criteria: Individual has at least one specified personal history feature (examples include: breast cancer diagnosed ≤50 years; metastatic breast cancer; multiple primary/bilateral breast cancers; triple-negative breast cancer; lobular breast cancer with personal or family history of diffuse gastric cancer; breast cancer with Ashkenazi Jewish ancestry; male breast cancer; unknown or limited family history with breast cancer; breast or prostate cancer with ≥1 first- or second-degree relative with a BRCA-related cancer; ovarian cancer (including fallopian tube or primary peritoneal cancer, sex-cord tumors with annular tubules, and/or hypercalcemic-type small cell carcinoma of the ovary); serous tubal intraepithelial carcinoma; pancreatic cancer; metastatic prostate cancer; neuroendocrine tumors (eg, adrenocortical carcinoma, paraganglioma, pheochromocytoma); malignant phyllodes tumors; renal cell carcinoma meeting specified criteria (diagnosed ≤46 years; bilateral or multifocal tumors; one or more first- or second-degree relatives with RCC; personal/family history of mesothelioma or uveal melanoma; or tumors with specified histologic features); at least two different primary solid tumors)

Individuals with a personal history of a Primary Solid Tumor — Family history or tumor indicators

Covered when ANY of the following family history or tumor-based indicators are present

Family history triggers: Individual has a personal history of a Primary Solid Tumor plus family-history patterns such as: at least one close blood relative with a Lynch-associated cancer; a close blood relative diagnosed ≤40 years; or at least two close blood relatives on same side with Primary Solid Tumors (excluding basal or squamous cell skin cancer)

Tumor-based triggers: Individual has a personal history of a Primary Solid Tumor plus tumor-based findings such as: a pathogenic variant detected in tumor tissue with potential germline implications (eg, BRCA1/2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C/D, RET, SDHAF2, SDHB/C/D, TMEM127, TSC2, VHL, APC, PTEN, RB1, TP53); or tumor demonstrating MSI-high or loss of mismatch repair protein expression; or renal tumor histology suggestive of hereditary RCC (multifocal papillary, FH-deficient/HLRCC-associated, Birt-Hogg-Dubé-related, angiomyolipomas with TSC features, succinate dehydrogenase-deficient RCC); or risk-model scores meeting thresholds (eg, Tyrer-Cuzick/BRCAPRO/CanRisk ≥2.5% for BRCA; PREMM5/MMRpro/MMRpredict ≥2.5% for Lynch)

Individuals with no personal history of a Primary Solid Tumor

Covered when AT LEAST one of the family history criteria or risk model thresholds are met

First-degree relative criteria: At least one first-degree relative with two or more different primary solid tumors, a Lynch-associated cancer, or a neuroendocrine tumor (eg, adrenocortical carcinoma, paraganglioma, pheochromocytoma)

First- or second-degree relative criteria: At least one first- or second-degree relative with early-onset breast cancer (≤50), triple-negative breast cancer, male breast cancer, metastatic prostate cancer, ovarian cancer, or pancreatic cancer

Second-degree relative criteria: At least one second-degree relative with two or more Lynch-associated cancers or a Lynch-associated cancer diagnosed ≤50 years

Extended family patterns: Family history patterns such as two or more second-degree relatives on same side with Lynch-associated cancers; two or more first- or second-degree relatives on same side with renal cell carcinoma; three or more close blood relatives on same side with any primary solid tumor; Ashkenazi Jewish ancestry with a close relative with a BRCA-related cancer; family member meeting polyposis criteria but unwilling/unable to test; or a first-degree relative meeting RCC evaluation criteria but unwilling/unable to test

Pediatric cancer

Cancer diagnosed ≤18: Multi-Gene hereditary cancer Panels are proven and medically necessary for individuals diagnosed with cancer at age 18 years or younger

Not covered / Unproven

Unproven tests: Multi-Gene Panels and related testing approaches are unproven and not medically necessary for indications other than those specified; concurrent RNA panel testing with DNA hereditary cancer panels, polygenic risk scoring for hereditary cancers, and whole-exome or whole-genome sequencing for identifying hereditary cancer syndromes or hereditary cancer syndrome risk are unproven and not medically necessary

General indications for hereditary cancer genetic testing

Genetic testing is generally recommended when ALL of the following are met

General testing prerequisites: (1) There is a personal or family history consistent with hereditary cancer susceptibility; (2) the test can be adequately interpreted (including appropriate laboratory methods and variant interpretation); and (3) test results can be used to diagnose or influence medical management of the individual or at-risk family members

Based on Robson et al., 2015 and descriptive policy text

Cancer- and gene-specific testing considerations

Gene- and cancer-specific considerations (examples, not exhaustive)

BRCA-related indications: BRCA1/2 testing is indicated for individuals with histories suggestive of hereditary breast and ovarian cancer, including early-onset breast cancer, ovarian cancer, pancreatic or prostate cancer in the context of family history, and populations with founder variants (eg, Ashkenazi Jewish ancestry); test approaches include sequence and duplication/deletion analysis or targeted founder testing as appropriate

Documented associated genes and testing approaches

Other gene indications: Testing for other high- and moderate-penetrance genes (eg, PALB2, TP53, CDH1, ATM, CHEK2, MLH1, MSH2, MSH6, PMS2, EPCAM, BRIP1, RAD51C/D) may be appropriate based on personal/family history and cancer type (breast, ovarian, colorectal, pancreatic, prostate); panel composition should prioritize genes with established clinical validity

Clinically Indicated Genetic Testing (NCCN/specialty guidance)

Covered when ANY of the following NCCN/society-specified clinical indications are met for the relevant cancer phenotype

General clinically indicated criteria (NCCN): Any blood relative with a known P/LP variant; prior limited negative testing with persistent phenotype where multigene testing is desired; tumor genomic testing identifies a variant with potential germline implications; testing will aid systemic therapy or surgical decision-making; or meets Li-Fraumeni/Cowden/Lynch syndrome testing criteria.

Breast cancer specific criteria: Personal history criteria: breast cancer diagnosed ≤50 years; testing at any age if used for PARP/olaparib treatment decisions; triple-negative breast cancer; multiple primaries; lobular breast cancer with family history of diffuse gastric cancer; male breast cancer; Ashkenazi Jewish ancestry; family patterns such as relative diagnosed ≤50, relative male breast cancer, relative with ovarian/pancreatic/high-risk prostate cancer, or ≥3 diagnoses on same side of family; unaffected individuals with a first- or second-degree relative meeting criteria or >5% BRCA probability.

Ovarian cancer specific criteria: Personal history of epithelial ovarian, fallopian tube, or peritoneal cancer at any age; certain nonepithelial ovarian cancers; unaffected individuals with a first- or second-degree relative with epithelial ovarian cancer; or >5% BRCA probability.

Lynch Syndrome Testing Criteria

Testing for Lynch syndrome is recommended when ANY of the following are met:

LS testing - known family variant: There is a known Lynch syndrome pathogenic/likely pathogenic variant in the family

LS testing - personal history with early onset or dMMR: Personal history of colorectal or endometrial cancer with age at diagnosis <50, or tumor showing dMMR/MSI-H, or another LS-related cancer, or synchronous/metachronous LS-related cancersage <50

LS testing - family history criteria: First- or second-degree relative with an LS-related cancer diagnosed <50, or two or more first- or second-degree relatives with LS-related cancers regardless of age, or other specified family clusters (eg, three or more relatives)

LS testing - predictive model or tumor/germline findings:

Adenomatous Polyposis Testing Criteria

Testing for adenomatous polyposis is recommended when ANY of the following are met:

Adenomatous polyposis - polyp burden: Personal history of 20 or more cumulative adenomas>=20 adenomas

Adenomatous polyposis - family variant: Family history of a known pathogenic variant in an adenomatous polyposis gene

Adenomatous polyposis - syndromic features: Multifocal/bilateral congenital hypertrophy of the retinal pigment epithelium, cribriform-morular variant of papillary thyroid cancer, or family history of polyposis with unwillingness/unable to test

Adenomatous polyposis - consider: Consider testing for desmoid tumor, hepatoblastoma, unilateral congenital hypertrophy of retinal pigment epithelium, serrated polyposis with adenomas, or 10-19 cumulative adenomas

Covered when guideline criteria are met

Covered when guideline-based criteria are met as outlined by ASCO and NCCN:

General ASCO recommendations: All patients with cancer should have a comprehensive family history recorded; offer germline multigene panel testing when indicated, ensuring panels include strongly recommended genes and balancing benefits versus harms; involve genetic expertise for ordering and interpretation

Tumor-to-germline triggers: Offer germline testing when tumor testing reveals pathogenic variants in specified genes (eg BRCA1/2, selected Lynch genes, SDHx, VHL, etc.), particularly in younger patients for some genes; tumor-detected PVs may prompt germline testing regardless of classic germline criteria

Cancer-specific NCCN recommendations: Germline multigene testing should be offered/considered per NCCN guidance for cancer types (prostate, pancreatic, renal, neuroendocrine/adrenal, pheochromocytoma/paraganglioma, etc.) when criteria (age, histology, family history, tumor features, or known familial PV) are met; panels should include at least listed genes relevant to the cancer type

Polygenic Risk Scores — evidence considerations

Evidence summaries and implied coverage stance

PRS clinical utility: PRS alone has modest discriminative ability (eg pooled AUC ~0.63 for prostate cancer) and improves when combined with clinical variables (AUC ~0.74); limited evidence, ancestry constraints, and uncertain impact on management limit routine clinical use

ACMG and systematic reviews highlight limitations and recommend caution

RNA testing — evidence considerations

Concurrent RNA testing with DNA hereditary cancer panels

RNA testing potential utility: RNA testing may clarify splicing-related variants and can increase diagnostic yield (example: a study reported a 9.1% relative increase in diagnostic yield), but currently evidence quality is limited and clinical impact on management is incompletely defined; more high-quality studies needed before routine concurrent RNA panels are recommended

WES/Exome+ — evidence considerations

Whole-exome sequencing for hereditary cancer risk assessment

WES findings vs guideline-based testing: Exome+/WES can detect carriers of HBOC and Lynch genes (eg, 1.24% carrier detection in a large cohort), including carriers who do not meet NCCN criteria; limitations include missed CNVs (5-25% of HBOC/LS PVs), language/access biases, and uncertainty about population screening utility

Individuals With a Personal History of a Primary Solid Tumor (renal cell carcinoma and related)

Revised covered indications include expanded specific criteria for certain tumor types.

Personal history - renal cell carcinoma specific criteria: Individual with renal cell carcinoma meets one or more of: diagnosed at age ≤46; diagnosed at any age with bilateral or multifocal tumors; one or more first- or second-degree relatives with renal cell carcinoma; personal or family history of mesothelioma or uveal melanoma; tumors with specific histologic features (multifocal papillary histology; hereditary leiomyomatosis-associated histology including FH deficiency; Birt-Hogg-Dubé-related histology; angiomyolipomas with additional tuberous sclerosis complex criterion; succinate dehydrogenase-deficient RCC histology)

Added as coverage triggers for multigene hereditary cancer panel testing

Serous tubal intraepithelial carcinoma

Serous tubal intraepithelial carcinoma: Presence of serous tubal intraepithelial carcinoma is an indication for multigene hereditary cancer panel testing

BRCA testing risk-model thresholds

BRCA1/2 risk threshold - personal history: Individual has a Tyrer-Cuzick, BRCAPRO, or CanRisk score ≥2.5% for a BRCA1/2 pathogenic variant2.5%

Replaced PENN11 with CanRisk in wording

BRCA1/2 risk threshold - no personal history: Individual has a Tyrer-Cuzick, BRCAPRO, or CanRisk score ≥5% for a BRCA1/2 pathogenic variant5%

Replaced PENN11 with CanRisk in wording

Basal cell and squamous cell skin cancers are specifically excluded from the policy’s definition of a Primary Solid Tumor for the purpose of hereditary cancer testing criteria. Multigene or BRCA testing coverage considerations that rely on a personal history of a Primary Solid Tumor do not apply when the only tumor(s) are basal or squamous cell skin cancers.

Broad, commercially offered multigene panels that include numerous low- or moderate-risk genes should be used with caution because they may identify variants of uncertain significance (VUS) or variants in genes with limited evidence to guide clinical management. Such findings can increase downstream testing, follow-up procedures, and potential overtreatment without clear benefit; order panels that are targeted to the clinical indication and include genes with established clinical validity whenever possible.

Pretest risk assessment and counseling, rather than universal testing, are the recommended approach for asymptomatic women. For women without a personal or family history or an ancestry associated with BRCA1/2 mutations, routine genetic counseling or BRCA testing is not indicated; screening tools and clinical evaluation should guide who is referred for counseling and potential testing.

The USPSTF recommends against routine genetic counseling or BRCA testing for women whose personal or family history and ancestry do not indicate an increased probability of a harmful BRCA1/2 mutation (Grade D). Screening with established family-history tools should be used to identify individuals who warrant counseling and possible testing.

Use of polygenic risk scores (PRS) to assess hereditary cancer susceptibility is not supported by sufficient evidence for routine clinical use. PRS approaches have limitations in discriminative performance and generalizability across populations and ancestry groups, and professional statements caution against using PRS as a standalone basis for hereditary cancer risk assessment or coverage decisions.

Current evidence is insufficient to support routine concurrent RNA panel testing alongside standard DNA-based BRCA1/2 or multigene hereditary cancer panels. While some studies report increased diagnostic yield when RNA analysis is added, study quality is limited and the impact on clinical management remains incompletely defined; RNA testing may be reasonable in select situations (e.g., to resolve a specific inconclusive DNA result) but is not supported for broad concurrent use.

Whole-exome sequencing (WES) or whole-genome sequencing (WGS), including Exome+ approaches, for the purpose of identifying hereditary cancer syndromes is considered unproven and not medically necessary for routine hereditary cancer risk assessment. Although exome-based screening can detect some carriers not identified by guideline-based testing, limitations (including variable detection of copy number variants and uncertain downstream clinical utility) mean WES/WGS is not supported as standard diagnostic or screening care for hereditary cancer at this time.

The policy explicitly lists several test types as not covered or unproven for hereditary cancer indications: concurrent RNA panel testing performed broadly with DNA hereditary cancer panels, polygenic risk scoring (PRS) for hereditary cancer assessment, and whole-exome/whole-genome sequencing (WES/WGS) for identifying hereditary cancer syndromes. Additionally, multigene panels performed outside the specified covered indications (for example, unselected population screening or panels including genes lacking evidence to change management) are considered unproven and not medically necessary.

Routine unselected population-wide multigene testing (population screening) using broad panels is not supported by current evidence. Large panels that include many genes with limited or disputed evidence reduce overall clinical utility in unselected individuals and may identify low-frequency findings of uncertain significance that do not clearly inform management.

Genetic testing in individuals without a personal or qualifying family history or ancestry that increases BRCA1/2 risk is not appropriate as routine population screening. Testing should follow risk assessment and be limited to persons whose personal/family history or validated risk-model thresholds indicate a meaningful probability of a pathogenic variant.

There is limited or minimal evidence supporting the routine use of comprehensive multisyndrome panels to directly guide clinical management in many contexts. Published analyses and guideline reviews note a paucity of outcome data comparing broad multisyndrome panels with targeted testing, and in some studies panel results did not clearly lead to documented management changes.

Ordering broad multigene panels without a clear clinical indication or without involvement of clinicians with appropriate genetic expertise increases the risk of identifying a high number of variants of uncertain significance (VUS). High VUS rates can prompt unnecessary follow-up testing, specialist referrals, or interventions with potential harms and additional cost; panels should be selected and interpreted with genetic expertise and documented clinical rationale to minimize these risks.

Whole-exome and whole-genome sequencing for the identification of hereditary cancer syndromes is considered not medically necessary for routine clinical evaluation. Although exome-based approaches can detect carriers not captured by guideline-directed testing, limitations in analytic completeness for certain variant types, uncertain clinical utility, and lack of guideline endorsement for population screening support a noncoverage stance for WES/WGS in this context.

Specific Covered Indications and Cancer-Type Criteria

Summary of covered indications

Summary of covered indications: Germline BRCA1/2 testing for breast cancer diagnosed ≤65 and multigene hereditary cancer panels when specified personal history, family history, tumor findings, or risk model thresholds are met; panels for pediatric cancer (≤18) are covered

Personal or family history consistent with hereditary cancer where results would influence management

Personal or family history consistent with hereditary cancer (breast, ovarian, colorectal, pancreatic, prostate) where test results would influence management; associated genes include BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53, ATM, BRIP1, RAD51C/D, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, CHEK2, HOXB13 and others

Patients meeting NCCN clinically indicated criteria for hereditary cancer testing (per cancer type)

Tests and Uses Not Covered / Considered Unproven

Summary: The policy does not cover routine RNA panel testing performed broadly with hereditary cancer panels, clinical use of polygenic risk scores (PRS) as a primary basis for hereditary cancer assessment, or WES/WGS for identifying hereditary cancer syndromes, and considers multigene panels outside the specified indications to be unproven/not medically necessary.

The policy does not support unselected, population-wide multigene panel testing that includes many genes with limited or disputed evidence of cancer association. Evidence indicates such unselected testing reduces clinical utility and increases detection of variants that lack clear guidance for management.

Routine population BRCA testing is not supported for individuals without a personal or qualifying family history or an ancestry associated with higher BRCA1/2 prevalence. Screening tools and targeted risk assessment are recommended to identify individuals who require counseling and possible BRCA testing.

There is limited evidence to support use of very broad multisyndrome panels as a routine tool to guide clinical management; available literature and guideline reviews note minimal or unclear support for some multisyndrome panel indications, and targeted testing is generally preferred when a specific syndrome is suspected.

Polygenic risk scores (PRS) are not supported as a primary assessment method for hereditary cancer risk due to insufficient and currently non-generalizable evidence. PRS may have modest predictive value in selected, well-characterized cohorts but lacks broad clinical validation and accepted pathways to change individual management.

Routine concurrent RNA panel testing with hereditary DNA panels is not supported by current evidence. While some studies show RNA testing can clarify certain splicing variants and increase diagnostic yield in select cohorts, evidence quality and impact on clinical management remain limited.

Applicable Procedure and Billing Codes

Applicable procedure 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/BRCA2 gene analysis; full sequence analysis and full duplication/deletion analysis (detection of large gene rearrangements).
81163	BRCA1/BRCA2 gene analysis; full sequence analysis.
81164	BRCA1/BRCA2 gene analysis; full duplication/deletion analysis (detection of large gene rearrangements).
0101U	Hereditary colon cancer disorders genomic sequence analysis panel utilizing NGS, Sanger, MLPA, and array CGH, with mRNA analytics when indicated [15 genes sequencing and deletion/duplication; EPCAM and GREM1 deletion/duplication only].
0102U	Hereditary breast cancer-related disorders genomic sequence analysis panel utilizing NGS, Sanger, MLPA, and array CGH, with mRNA analytics when indicated [17 genes sequencing and deletion/duplication].
0103U	Hereditary ovarian cancer genomic sequence analysis panel utilizing NGS, Sanger, MLPA, and array CGH, with mRNA analytics when indicated [24 genes sequencing and deletion/duplication; EPCAM deletion/duplication only].
0129U	Hereditary breast cancer-related disorders genomic sequence and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, TP53).
0130U	Targeted mRNA sequence analysis panel for hereditary colon cancer disorders (APC, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, TP53) (List separately).
0133U	Hereditary prostate cancer-related targeted mRNA sequence analysis panel (11 genes) (List separately).

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Applicable molecular/exome/genome codesmixed

0212U	Rare diseases (constitutional/heritable disorders), whole genome and mitochondrial DNA sequence analysis, including small sequence changes, deletions, duplications, short tandem repeat expansions, and variants in non-uniquely mappable regions, identification and categorization of genetic variants.
0213U	Whole genome and mitochondrial DNA sequence analysis, identification and categorization of genetic variants, each comparator genome (e.g., parent, sibling).
0214U	Whole exome and mitochondrial DNA sequence analysis, proband, identification and categorization of genetic variants.
0215U	Whole exome and mitochondrial DNA sequence analysis, each comparator exome (e.g., parent, sibling).
0265U	Whole genome and mitochondrial DNA sequence analysis, blood, frozen and FFPE tissue, identification of SNVs and CNVs.
0266U	Tissue-specific gene expression by whole-transcriptome NGS; presence or absence of splicing or expression change.
81415	Exome; sequence analysis.
81416	Exome; sequence analysis, each comparator exome (List separately).
81417	Exome; re-evaluation of previously obtained exome sequence.
81425	Genome; sequence analysis.

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Removed Multigene Panel CPT CodesCPT

0131U	Removed CPT code
0132U	Removed CPT code
0135U	Removed CPT code

Added WES/WGS and related CPT CodesCPT

0212U	Added CPT code (Whole genome and mitochondrial DNA sequence analysis).
0213U	Added CPT code (Whole genome and mitochondrial DNA sequence analysis, each comparator genome).
0214U	Added CPT code (Whole exome and mitochondrial DNA sequence analysis, proband).
0215U	Added CPT code (Whole exome and mitochondrial DNA sequence analysis, each comparator exome).
0265U	Added CPT code (Whole genome and mitochondrial DNA sequence analysis, identification of SNVs and CNVs).
0266U	Added CPT code (Whole-transcriptome tissue-specific gene expression by NGS).
81415	Added CPT code (Exome sequence analysis).
81416	Added CPT code (Exome sequence analysis, each comparator exome).
81417	Added CPT code (Re-evaluation of previously obtained exome sequence).
81425	Added CPT code (Genome sequence analysis).

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inv-36: Risk model thresholds (summary of models and % cutoffs)

BRCA1/2 — personal history thresholdTyrer-Cuzick, BRCAPRO, or CanRisk ≥2.5% probability

BRCA1/2 — no personal history thresholdTyrer-Cuzick, BRCAPRO, or CanRisk ≥5% probability

Lynch syndrome — personal history thresholdPREMM5, MMRpro, or MMRpredict ≥2.5% probability (contexts with personal tumor findings)

Lynch syndrome — no personal history thresholdPREMM5, MMRpro, or MMRpredict ≥5% probability

inv-37: BRCA1/2 risk model thresholds — 2.5% (personal history) and 5% (no personal history) using Tyrer-Cuzick, BRCAPRO, or CanRisk

Provider Actions, Documentation, and Prior Authorization

Billing Rule

Applicable codes listed

The following codes are provided for reference and may be subject to prior authorization per contract. Listing a code does not guarantee coverage or payment.

Applicable procedure and molecular pathology codes are included for reference only.
Inclusion of a code does not imply coverage; federal, state, or contractual benefit requirements govern.

Prior Authorization

Prior authorization for RNA/WES-related testing

Prior authorization is required for requests involving concurrent RNA/transcriptome testing or whole-exome/whole-genome (WES/WGS) testing when submitted for hereditary cancer evaluation. Submitters should expect review of clinical rationale and supporting documentation.

Eligibility Requirements and Coverage Preconditions

Coverage for individuals without a personal history of cancer requires detailed and specific family history patterns. Acceptable family-history triggers include multi-relative clusters of relevant cancers (for example, multiple first- or second-degree relatives with Lynch-associated cancers, multiple relatives with renal cell carcinoma on the same side of the family, Ashkenazi Jewish ancestry with a close relative having a BRCA-related cancer, or a relative meeting polyposis criteria but unwilling/unable to test). Documentation of degree of relation, ages at diagnosis, and primary sites is required to support medical necessity.

A detailed pedigree including first-, second-, and third-degree relatives with ages at diagnosis and primary cancer sites must accompany requests when testing is sought on the basis of family history. The clinical record should document that the family pattern meets one of the policy’s specified family-history thresholds before coverage is considered.

For Lynch syndrome–related indications, predictive model scores (e.g., PREMM5, MMRpro, MMRpredict) and tumor dMMR/MSI status are acceptable criteria for selecting individuals without a personal history of cancer; a model score threshold of 5% is generally used for unaffected individuals, with lower thresholds (≥2.5%) applied in some specific clinical contexts per guideline guidance.

When family history or tumor-based triggers are absent, BRCA1/2 testing may still be covered if validated risk-model thresholds are met. The policy specifies use of Tyrer-Cuzick, BRCAPRO, or CanRisk with thresholds of ≥2.5% for some personal-history contexts and ≥5% for unaffected individuals without a personal cancer history.

Testing should be ordered by or in consultation with clinicians experienced in hereditary cancer risk assessment and genetic testing (for example, genetic counselors, oncologists, or other specialists familiar with guideline-based indications). Orders should document how testing will influence diagnosis or management and include prior relevant testing results when applicable.

Definitions and Key Terms

inv-69: Multi-Gene Panel definition — tests using NGS to test multiple genes; multi-gene panel = 5+ genes per policy threshold

DefinitionGenetic tests using next-generation sequencing to test multiple genes simultaneously; for this policy a Multi-Gene Panel consists of five or more genes

Typical contentOften include sequencing plus large deletion/duplication (CNV) analysis

Test rationaleUsed when multiple hereditary cancer genes are under consideration or when family/tumor features indicate broader evaluation

inv-70: BRCA-Related Cancers — list of cancers related to BRCA genes

BRCA-related cancersBreast cancer

BRCA-related cancersOvarian/fallopian tube/primary peritoneal cancer

Background and Evidence Summary

Background: Hereditary cancer testing identifies germline pathogenic or likely pathogenic (P/LP) variants associated with increased cancer risk. Testing options include single-gene tests, known familial mutation testing, and multigene hereditary cancer panels (MGPT) that use next-generation sequencing to evaluate multiple genes simultaneously. Selection of the appropriate test is guided by personal and family history, tumor findings, and validated risk models.

Policy Revision History

2026-05-01policy_modifiedLatest

Revised coverage criteria for multigene hereditary cancer panels: added serous tubal intraepithelial carcinoma as an indication and expanded renal cell carcinoma-specific triggers (age ≤46, bilateral/multifocal tumors, family history, mesothelioma/uveal melanoma history, and specified histologic features); replaced PENN11 with CanRisk in BRCA1/2 risk-model wording; clarified ovarian cancer examples.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer (for Pennsylvania Only)

Policy CodePolicy CS049PA.W

Change TypeCriteria and coding revisions

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionDocument clinical indication, family history, and pedigree when requesting multigene hereditary cancer testing; prior authorization may be required for listed codes.

SourceLink

On This Page

Risk model thresholds: Risk models meeting higher thresholds (eg, Tyrer-Cuzick/BRCAPRO/CanRisk ≥5% for BRCA1/2; PREMM5/MMRpro/MMRpredict ≥5% for Lynch)

Pancreatic cancer specific criteria: Personal history of exocrine or neuroendocrine pancreatic cancer; first-degree relative with exocrine pancreatic cancer; or neuroendocrine pancreatic tumor.

Prostate cancer specific criteria: Personal history of metastatic or high/very-high risk prostate cancer; family/ancestry features (eg close relative with breast cancer ≤50, male breast cancer, ovarian or pancreatic cancer, metastatic/high-risk prostate cancer); ≥3 close relatives with breast/prostate cancer on same side; Ashkenazi Jewish ancestry; or unaffected with first-degree relative meeting criteria.

Predictive model score ≥5% (eg PREMM5, MMRpro) or personal tumor dMMR at any age or personal history of a P/LP variant found on tumor testing with potential germline implication; note: PREMM5/MMRpro/MMRpredict ≥2.5% may be used in certain contexts

>=5% (or >=2.5% in specified contexts)

10-19 adenomas (consider)

NCCN clinically indicated patients:

Patients meeting NCCN clinically indicated criteria for hereditary breast, ovarian, pancreatic, or prostate cancer testing (by cancer type, age at diagnosis, histology, family history, tumor PVs, or known familial PV); includes testing to inform systemic therapy or surgical decision-making and when a known familial P/LP variant exists

All patients with epithelial ovarian cancer should undergo germline testing for BRCA1/2 and other ovarian susceptibility genes

Epithelial ovarian cancer: All patients with epithelial ovarian cancer should undergo germline testing for BRCA1/2 and other ovarian susceptibility genes

CRC patients — MGPT may identify clinically actionable variants

CRC patients - MGPT utility: Patients with colorectal cancer undergoing evaluation where germline multigene panel testing may identify clinically actionable P/LP variants; studies report clinically actionable variant rates (eg, 14.2% with ≥1 P/LP in one large MGPT CRC cohort)

Germline MGPT for CRC/EC — minimum gene set and clinical rationale

MGPT for CRC/EC - minimum gene set: Germline MGPT for colorectal or endometrial cancer should include at minimum specified CRC genes (APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM, BMPR1A, SMAD4, PTEN, STK11, TP53) and for EC include MLH1, MSH2, MSH6, PMS2, EPCAM, PTEN, BRCA1/2; document clinical rationale (age, phenotype, polyps, family history, tumor dMMR) when ordering

MGPT for gastrointestinal hamartomatous polyposis syndromes and related conditions

MGPT for hamartomatous polyposis syndromes: Genetic evaluation and MGPT for gastrointestinal hamartomatous polyposis syndromes, Peutz-Jeghers, juvenile polyposis, and related syndromes when clinical thresholds are met

MGPT for pancreatic cancer and select unselected solid tumors

MGPT for pancreatic and select unselected tumors: MGPT for pancreatic cancer and select unselected solid tumors may identify clinically actionable pathogenic germline variants and impact treatment decisions; studies report ~15% PGV prevalence in pancreatic cancer and ~13.3% in mixed unselected solid tumor cohorts

MGPT for pheochromocytoma/paraganglioma (PPGL)

MGPT for PPGL: MGPT targeted to pheochromocytoma/paraganglioma is recommended due to high diagnostic yield; panels should include SDHx, VHL, RET, NF1, TMEM127, MAX and others

Patients who meet ASCO/NCCN criteria by cancer type, age, histology, family history, tumor PVs, or known familial PV

ASCO/NCCN criteria met: Patients with cancer who meet ASCO or NCCN criteria by cancer type, age at diagnosis, histology, family history, tumor PVs, or known familial PV should be offered germline testing with panels that include listed relevant genes

Exome+ findings — broader detection but not universal screening

Exome+ detection nuance: Exome+ sequencing can identify HBOC and Lynch carriers including individuals who do not meet NCCN criteria, but findings do not establish universal screening as standard and exome approaches may miss CNVs

Individuals with a personal history of a primary solid tumor meeting specified criteria

Personal history criteria (general): Individuals with a personal history of a primary solid tumor (excluding basal or squamous cell skin cancer) meeting specified tumor-specific or family history criteria (including expanded renal cell carcinoma histology and family-history based triggers; serous tubal intraepithelial carcinoma added) are covered for germline testing

Whole-exome and whole-genome sequencing (WES/WGS) for routine identification of hereditary cancer risk is considered unproven and is not covered for this indication. Exome+ cohorts have detected carriers outside guideline-based testing groups, but limitations in analytic completeness and uncertain downstream utility support a noncoverage position.

BRCA1/2 — personal historyTyrer-Cuzick, BRCAPRO, or CanRisk score ≥2.5%

BRCA1/2 — no personal historyTyrer-Cuzick, BRCAPRO, or CanRisk score ≥5%

Risk models specifiedAcceptable models: Tyrer-Cuzick, BRCAPRO, CanRisk

Prior authorization required for concurrent RNA panel testing with BRCA1/2 or multigene panels.
Prior authorization required for Exome (81415, 81416, 81417) and Genome (81425–81427) services and related PLA codes (0212U–0215U, 0265U–0266U).
Requests lacking adequate documentation may be delayed or denied.

Billing Rule

WES/WGS coding and prior authorization

WES and WGS CPT/PLA codes have been added to the applicable code list, but germline WES/WGS for routine hereditary cancer syndrome identification is considered unproven and not medically necessary per policy. Authorization may be denied if clinical utility is not demonstrated for the individual.

Added codes: 0212U, 0213U, 0214U, 0215U, 0265U, 0266U, 81415–81417, 81425–81427.
Coverage for WES/WGS to identify hereditary cancer syndromes is considered unproven and not medically necessary; prior authorization does not imply approval.

Prior Authorization

NCCN-based indication requirement

Testing should follow NCCN clinical criteria: multigene testing is clinically indicated only when personal or family history meets NCCN guideline indications. Absent appropriate NCCN-based history, testing may not be indicated.

Indications include: known family P/LP variant, tumor finding with germline implications, testing to guide systemic therapy or surgery, and specific syndrome criteria (e.g., Li-Fraumeni, Cowden, Lynch).
Testing may be considered (but not always indicated) in select ancestry or phenotype contexts per NCCN.

Prior Authorization

USPSTF limitation on routine BRCA testing

USPSTF recommends screening primary-care patients for family/personal history that suggests increased BRCA risk and counseling/testing only when indicated; it recommends against routine BRCA counseling or testing for average-risk women without relevant history or ancestry.

Use validated screening tools (e.g., Manchester, Pedigree Assessment Tool, Tyrer-Cuzick, BRCAPRO) to identify candidates for genetic counseling/testing.
Routine BRCA testing is not recommended for women without a personal/family history or ancestry associated with increased BRCA1/2 risk.

Documentation Required

Expertise & interpretation risk

Ordering clinicians should involve or consult genetic expertise when using multigene panels or interpreting complex results to mitigate misinterpretation and inappropriate management.

Genetic counselors or genetics specialists are recommended for pre- and post-test counseling and result interpretation.
Expertise is particularly important for large panels, variants of uncertain significance (VUS), PRS interpretation, and treatment-directed testing.

Denial Risk

RNA testing evidence limitations

Current evidence is insufficient to support routine concurrent RNA panel testing with DNA-based hereditary cancer panels. RNA testing may clarify some variants but should be used selectively with documented rationale.

RNA panel testing (e.g., 0266U) may increase diagnostic yield in select cases but quality of evidence is limited.
Provide specific justification for concurrent RNA testing (e.g., variant of uncertain significance requiring splicing assessment).

Denial Risk

WES/WGS noncoverage

WES/WGS used to screen broadly for hereditary cancer syndromes is considered unproven and not medically necessary under this policy. Authorization requests must demonstrate clinical necessity beyond broad population screening.

WES/WGS codes included for reference, but routine germline WES/WGS for HBOC/LS identification is not covered as standard of care.
Requests for WES/WGS will be reviewed for documented clinical utility; lack thereof may result in denial.

Documentation Required

Required medical records and pedigree

Requests for genetic testing and prior authorization must include contemporaneous medical records and a pedigree (personal and family history drawing) using standardized nomenclature.

Include a legible pedigree diagram showing at least first-, second-, and third-degree relatives, ages at diagnosis, and relevant cancers.
Attach relevant medical history, physical exam findings, and results of prior genetic or tumor testing.

Prior Authorization

Required clinical documentation for testing

Prior authorization submissions should include detailed clinical documentation: personal and family history, rationale for the chosen test/panel, and how results will affect management or cascade testing.

Document the clinical indication, specific genes/panel requested and why, and anticipated impact on treatment/surveillance.
If testing follows tumor findings or will guide systemic therapy, include pathology/tumor genomic results.

Documentation Required

History and counseling documentation

Document pretest counseling, discussion of benefits/limitations, psychosocial assessment, and consent; record post-test counseling and management plan when applicable.

Record that genetic counseling occurred (or is planned) and summarize the counseling content, including discussion of VUS and potential downstream implications.
Include results of any risk assessment tools used (e.g., BRCAPRO, Tyrer-Cuzick, PREMM5).

Documentation Required

Laboratory and counseling documentation

Provide laboratory-level information and counseling notes: test name, laboratory, exact genes/exons analyzed, methodology (sequencing + deletion/duplication), and notation of large rearrangement testing workflow.

Specify panel composition and rationale because commercially available panels vary substantially.
Indicate whether large rearrangement (LR) testing is included or will be reflexed; for high-risk BRCA individuals LR testing is frequently performed concurrently with sequencing, while elective cases may reflex to LR testing only if sequencing is negative.

Documentation Required

Documentation for Exome+ results

When Exome+ or population-scale exome reports are used to identify HBOC/Lynch carriers, include a chart review documenting personal and family cancer history, and evidence that the identified variant correlates with clinical criteria or will change management.

Include a focused chart review showing whether the individual meets NCCN testing criteria and how the result will affect clinical care or cascade testing.
Document limitations of exome-based approaches (e.g., lower sensitivity for copy number variants) in the record.

Note

Large rearrangement testing workflow

Testing strategy for large rearrangements (LRs) may differ by risk group: high-risk individuals often receive LR testing concurrently with sequencing; elective or lower-risk individuals may have LR testing reflexed only after negative sequencing results.

If ordering for a high-risk BRCA individual, document that LR analysis is included with sequencing or provide rationale if not.
If LR testing will be reflexed, document the reflex criteria and timeline.

Note

Panel vs targeted testing consideration

Favor targeted (syndrome-directed) testing when a single syndrome is most likely; use multigene panels when multiple syndromes are possible or when prior testing was limited. Consider smaller panels when rapid treatment decisions are needed.

Use syndrome-directed gene analysis when clinical features point clearly to one hereditary syndrome.
Use MGPT when multiple genes could explain the phenotype or when prior limited testing was negative and further evaluation is warranted.
For urgent therapeutic decisions, order smaller targeted panels first; larger panels may be run subsequently if needed.

Step Therapy

Step therapy

There are no step therapy requirements specified in this policy for hereditary cancer genetic testing; however, testing should follow documented clinical indications and benefit plan rules.

No step therapy mandates for ordering multigene panels or BRCA/LS testing are defined in this policy.
Clinical necessity and contractual benefit terms govern coverage decisions.

Individuals previously tested with limited or single-gene testing who continue to meet clinical criteria (for example, bilateral breast cancer or breast cancer with a close relative with ovarian cancer) may be candidates for subsequent multigene panel testing; documentation of prior testing and rationale for expanded testing should be provided.

When ordering multigene panels for colorectal or endometrial cancer indications, include at minimum the CRC/EC-related genes recommended by NCCN and document the clinical rationale (age, phenotype, tumor dMMR status, or predictive model score) supporting the panel composition.

Requests must be accompanied by contemporaneous medical records supporting the indication, including a pedigree and relevant diagnostic test results. Incomplete documentation that does not clearly support medical necessity may result in denial.

When Exome+ or other exome-based results are used, the policy expects chart review and documentation of personal and family history to contextualize findings; exome findings that lack clinical context or do not meet guideline-based criteria may not justify coverage for further hereditary-cancer-directed interventions.

Panel selection should be justified in the medical record, noting the genes included and the reason those genes were selected based on the patient’s phenotype and family history. Because commercially available panels vary, documentation of clinical rationale helps ensure appropriate test choice and interpretation.

Family history documentation must include degree of relation, ages at diagnosis, and primary tumor sites; this information is essential to apply the policy’s family-history thresholds and risk-model criteria accurately.

For renal cell carcinoma indications, documented tumor histology, age at diagnosis, and presence of bilateral or multifocal disease are important eligibility elements; these details must be present in the record to justify multigene panel testing for RCC-related triggers.

Pretest genetic counseling is strongly recommended and should be documented in the medical record. Counseling helps ensure that patients understand the advantages, limitations, and potential downstream consequences of testing, including the possibility of VUS results.

Genetic testing is ideally ordered with professional genetic expertise; when tests include genes of uncertain management implications, involvement of genetic professionals for ordering and interpretation is particularly important and should be documented.

Documentation should demonstrate how test results would influence clinical management for the patient or at-risk family members; tests ordered that are unlikely to change care are less likely to meet medical necessity criteria.

If RNA testing is requested to clarify a previously inconclusive DNA result, documentation of the prior DNA test and rationale for RNA analysis should be provided. Routine concurrent RNA testing without such context is not supported by current evidence.

BRCA-related cancersPancreatic adenocarcinoma

BRCA-related cancersProstate cancer

inv-71: Limited Family History definition

DefinitionFewer 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 or limited pedigree)

ImplicationMay trigger testing when family history is limited and individual personal risk features present

inv-72: Hereditary cancer susceptibility testing definition

DefinitionGenetic testing to predict an individual's inherited risk of developing cancer, informed by personal and family history and intended to guide diagnosis or medical management

PurposeIdentify germline pathogenic variants that affect individual and familial medical management

inv-73: Multi-gene panel (MGPT) definition — commercial panels testing multiple genes including CNV detection

DefinitionCommercial panels that test multiple genes simultaneously for hereditary cancer predisposition; often include large deletion/duplication (CNV) analysis

ConsiderationPanel composition varies; inclusion of low/moderate-risk genes may yield variants of uncertain management impact

inv-74: MGPT definition (alternate) — NGS panels evaluating multiple hereditary cancer genes

DefinitionNext-generation sequencing panels evaluating multiple hereditary cancer genes simultaneously for germline risk assessment

Best practiceTesting should include sequencing and deletion/duplication analysis when applicable and be ordered with genetic expertise

inv-75: P/LP variant definition — pathogenic or likely pathogenic germline variant

DefinitionA pathogenic or likely pathogenic (P/LP) germline variant is a genomic alteration classified as pathogenic or likely pathogenic and associated with increased hereditary cancer risk

Clinical implicationIdentification of a P/LP variant can direct management for the individual and cascade testing for relatives

inv-76: Lynch syndrome definition and associated genes

DefinitionLynch syndrome is defined by germline heterozygous P/LP variants in mismatch repair genes MLH1, MSH2, MSH6, PMS2, or 3' EPCAM deletions

Associated cancersIncreased risk for colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, small bowel, sebaceous neoplasms, biliary tract, and certain brain cancers

inv-77: MGPT — germline multigene panel testing definition

DefinitionGermline multigene panel testing using next-generation sequencing to evaluate multiple hereditary cancer susceptibility genes simultaneously

Panel selectionPanel content should include genes relevant to the cancer phenotype and be chosen with genetic expertise

inv-78: Polygenic Risk Score (PRS) — definition

DefinitionA Polygenic Risk Score (PRS) is an aggregated measure of risk based on the combined effect of many genetic variants (SNPs), some not tied to known genes for the condition

LimitationCurrent evidence is insufficient to support PRS as a standalone basis for hereditary cancer risk assessment; ancestry and generalizability limitations exist

inv-79: PRS extended definition — combined SNP metric to stratify risk

Extended definitionA combined metric derived from multiple single-nucleotide polymorphisms intended to stratify genetic risk for common diseases (e.g., prostate, breast cancer)

Clinical notePRS performance improves when combined with clinical variables but remains limited by study populations and evidence quality

inv-80: Concurrent RNA panel testing definition

DefinitionRNA sequencing performed concurrently with DNA-based hereditary cancer panel testing to assess splicing and transcript-level effects of variants

EvidenceMay clarify some variants and modestly increase diagnostic yield (example: 9.1% relative increase) but evidence is insufficient for routine concurrent use

inv-81: Exome+ / WES definition

DefinitionSequencing of the protein-coding regions of the genome (exome) used to detect single-nucleotide variants and small indels in genes associated with hereditary cancer syndromes

LimitationMay not reliably detect copy-number variants (CNVs) which account for 5%–25% of pathogenic variants in HBOC/LS; population screening utility unproven

inv-82: Primary Solid Tumor definition (updated reference)

DefinitionPrimary Solid Tumor: an abnormal mass of tissue, typically solid (no cysts/liquid), that is the original tumor from which metastases may arise

Exclusion noteBasal or squamous cell skin cancers are excluded from Primary Solid Tumor consideration for hereditary cancer testing criteria

inv-83: Risk models — CanRisk, Tyrer-Cuzick, BRCAPRO specified for BRCA thresholds

Risk models specified for BRCA1/2Tyrer-Cuzick, BRCAPRO, CanRisk

UsageModels are used to generate 2.5% (personal history) or 5% (no personal history) probability cutoffs for BRCA1/2 testing consideration