ModifiedUnitedHealthcarePolicy CS049.Z

Genetic Testing for Hereditary Cancer

UnitedHealthcare clinical policy governing coverage criteria for germline genetic testing for hereditary cancer susceptibility and who it affects (patients and ordering providers). Applies nationally except where state-specific policies are noted.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer

Policy CodePolicy CS049.Z

Change TypeCoverage criteria revisedadded exclusions

Effective DateJun 1, 2025

Next Review Date

Key ActionDocument pedigree, family history, and genetic counseling and verify prior authorization/benefit terms before submitting testing requests.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria for genetic testing with a Multi-Gene hereditary cancer Panel for individuals with a personal history of a Primary Solid Tumor, including added and replaced specific criteria.

Revised coverage criteria for individuals with no personal history of a Primary Solid Tumor, replacing several relative-history criteria and adding new required criteria.

Added language that genetic testing for polygenic risk scoring for hereditary cancers is unproven and not medically necessary for all indications.

Added CPT code 0495U to Applicable Codes.

Removed content/language pertaining to the state of Louisiana.

5-10%Estimated hereditary cancers

>=5 genesMulti-Gene Panel threshold

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.

≤65BRCA testing age

PREMM5 ≥2.5%/≥5%PREMM5/MMR threshold

Not coveredPRS stance

Coverage Criteria and Clinical Indications

Medical necessity criteria

Covered when ALL of the following are met according to the group below (organized by personal history status):

Individuals with personal history of Primary Solid Tumor: Genetic testing with a Multi-Gene hereditary cancer Panel for individuals with a personal history of a Primary Solid Tumor (excluding basal or squamous cell skin cancer) is proven and medically necessary when the individual meets at least one of the following personal-history criteria: breast cancer diagnosed ≤50 years; metastatic breast cancer; multiple primary breast cancers (including bilateral); 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 or prostate cancer with at least one first- or second-degree relative with a BRCA-related cancer; ovarian cancer (including fallopian tube or primary peritoneal cancer); pancreatic cancer; metastatic prostate cancer; cancers associated with Lynch syndrome; neuroendocrine tumors (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma); malignant phyllodes tumors; or at least two different primary solid tumors (excluding basal or squamous cell skin cancer).1+ criteria

Individuals with personal history + family history: Genetic testing with a Multi-Gene hereditary cancer Panel is proven and medically necessary when an individual with a personal history of a Primary Solid Tumor has family-history features including at least one close blood relative with a Lynch-syndrome cancer; a close relative diagnosed ≤40 years with a primary solid tumor; two or more close blood relatives on the same side with primary solid tumors; OR when tumor testing demonstrates a pathogenic variant with germline implications, MSI-high/dMMR, or elevated predictive-model scores (Tyrer-Cuzick/BRCAPro/Penn11 ≥2.5% for BRCA1/2 or PREMM5/MMRpro/MMRpredict ≥2.5% for Lynch genes).1+ criteria

Individuals without personal history (family-history criteria): Genetic testing (multi-gene panel or BRCA1/2) is proven and medically necessary for individuals with no personal history of a Primary Solid Tumor when family history meets at least one of these patterns: a first-degree relative with two or more different primary solid tumors or a Lynch-syndrome cancer or a neuroendocrine tumor; a first- or second-degree relative with breast cancer ≤50, triple-negative breast cancer, breast cancer in an individual assigned male at birth, metastatic prostate cancer, ovarian cancer (including fallopian tube or primary peritoneal), or pancreatic cancer; a second-degree relative with two or more Lynch-syndrome cancers or a Lynch-syndrome cancer diagnosed ≤50; two or more second-degree relatives on the same side with Lynch-syndrome cancers; three or more close blood relatives on same side with primary solid tumors; Ashkenazi Jewish ancestry plus at least one close relative with a BRCA-related cancer; family member meeting polyposis diagnostic criteria who is unwilling/unable to test; personal family history of colorectal polyposis with ≥10 adenomas; or elevated predictive-model thresholds (BRCA models ≥5% or PREMM/MMR models ≥5%).1+ criteria

Pediatric cancer: Multi-Gene hereditary cancer Panels are proven and medically necessary for individuals diagnosed with cancer at age 18 years or younger.age <=18

Not covered indications: Multi-Gene hereditary cancer Panels are unproven and not medically necessary for other indications not listed above; RNA panel testing for hereditary cancers and genetic testing for the purpose of polygenic risk scoring for hereditary cancers are unproven and not medically necessary for all indications.

ASCO/SSO germline testing recommendations

ASCO/SSO 2024 recommendations for germline BRCA1/2 testing in individuals with breast cancer

BRCA testing for newly diagnosed individuals <=65: Offer BRCA1/2 testing to individuals 65 years of age or younger with newly diagnosed breast cancer (stage I–III or de novo stage IV).age <= 65

BRCA testing for individuals >65: Offer BRCA1/2 testing to individuals older than 65 with breast cancer if any of the following apply: candidate for PARP inhibitor therapy, triple-negative breast cancer, personal or family history suggesting a pathogenic variant, assigned male sex at birth, or Ashkenazi Jewish or other founder-population ancestry.

Extended testing: Individuals undergoing BRCA1/2 testing should be offered testing for other hereditary cancer predisposition genes determined by individual or family history.

ASCO testing criteria

ASCO and ASCO policy statements supporting testing when clinical utility and interpretability exist

ASCO three-criteria: Recommend genetic testing when all of the following are met: (1) the individual has a personal or family history suggestive of genetic cancer susceptibility; (2) the test can be adequately interpreted; and (3) test results have accepted clinical utility.

ACOG indications

ACOG guidance for who should be considered for genetic evaluation/testing

ACOG indications: Refer for genetic evaluation or testing when hereditary cancer risk assessment suggests increased risk, including: close relative with known BRCA mutation; personal histories such as ovarian cancer, breast cancer ≤45 (or ≤50 in other guidance), triple-negative breast cancer ≤60, Ashkenazi Jewish ancestry; male breast cancer in a relative; multiple relatives meeting criteria for hereditary breast/ovarian cancer; or strong family histories suggestive of HBOC or Lynch syndrome.

ACMG position

ACMG position on universal testing

ACMG evaluation: ACMG recommends evaluation of all patients with breast cancer for the need for germline genetic testing but cautions that current evidence does not support testing every individual with broad multigene panels that include genes lacking evidence to change management; when testing is performed it should include full sequencing and deletion/duplication analysis in an accredited laboratory and be accompanied by genetic counseling.

Clinically Indicated Testing

Covered when ANY of the following NCCN/NCCN-aligned clinically indicated situations are met for respective cancer types

General clinically indicated testing (NCCN): Clinically indicated when: a blood relative has a known P/LP variant; prior limited negative testing and patient desires multigene testing; a P/LP variant identified on tumor genomic testing with germline implications; testing to inform systemic therapy or surgical decisions; or when the individual meets specific syndrome criteria (e.g., Li-Fraumeni, Cowden/PTEN, Lynch syndrome).

Breast cancer-specific clinically indicated criteria: Indications include breast cancer diagnosed ≤50 years; testing to guide PARP/olaparib therapy; triple-negative histology; multiple primaries; male breast cancer; Ashkenazi Jewish ancestry; or family-history features (close relatives with early breast cancer, male breast cancer, ovarian/pancreatic/metastatic prostate cancer), or a prior probability >5% for BRCA1/2.

Ovarian cancer-specific clinically indicated criteria: Indication: personal history of epithelial ovarian/fallopian tube/primary peritoneal cancer at any age, or unaffected individuals with a first- or second-degree relative with epithelial ovarian cancer, or BRCA1/2 probability >5% by prior models. Germline testing for BRCA1/2 and ovarian susceptibility genes is recommended; if germline BRCA1/2 negative, perform somatic tumor BRCA1/2 testing.

Lynch syndrome (LS) testing — covered when ANY of the following are met

Testing for LS is recommended when ANY of the following are present:

LS testing indications: Indications include: known LS pathogenic variant in the family; individual with LS-related cancer diagnosed ≤49 years; synchronous/metachronous LS-related cancers; first- or second-degree relative with LS-related cancer diagnosed ≤49 years; two or more first- or second-degree relatives with LS-related cancers; family-history patterns (one+ first-degree CRC/EC <50, two+ relatives with LS cancers including one <50, three+ relatives with LS cancers); predictive model risk ≥5% (PREMM5/MMRpro/MMRpredict) — note PREMM5 ≥2.5% may be used in certain contexts; personal tumor dMMR (MSI-high or abnormal IHC); or tumor-detected P/LP variant with germline implications.

Adenomatous polyposis testing — covered when ANY of the following are met

Testing for adenomatous polyposis is recommended when ANY of these are present:

APC/adenomatous polyposis indications: Indications include: personal history of ≥20 cumulative adenomas; family history of a known pathogenic variant in adenomatous polyposis genes; multifocal/bilateral CHRPE; cribriform-morular variant of papillary thyroid cancer; family history of polyposis with inability/unwillingness to test. Consider testing for 10–19 adenomas and other listed situations; tumor-detected APC P/LP variants should prompt consideration of germline testing in appropriate contexts.

Hamartomatous polyposis / Peutz-Jeghers / juvenile polyposis testing

Genetic evaluation and MGPT recommended when criteria met:

Hamartomatous polyposis indications: Indications to perform genetic evaluation and multigene panel testing include: two or more lifetime hamartomatous polyps; family history of hamartomatous polyps or associated cancer in first- or second-degree relative; two or more histologically confirmed Peutz–Jeghers polyps; any Peutz–Jeghers polyp with family history or characteristic mucocutaneous pigmentation; five or more juvenile polyps of colon/rectum; two or more juvenile polyps elsewhere; juvenile polyps plus first-degree relative with juvenile polyposis. MGPT is recommended when testing indicated.

ASCO recommendations for germline MGPT in individuals with cancer

ASCO recommends offering germline multigene panels when indicated and including key genes:

ASCO panel guidance: All individuals with cancer should have comprehensive family history recorded. When germline testing is indicated, offer MGPT that includes at minimum the more strongly recommended genes for the cancer type; panels may include less strongly recommended genes when appropriate. Smaller panels may be applied initially if rapid results are needed for treatment decisions; broader panels may be ordered when benefits are identified.

Guideline-recommended gene lists by cancer type

ASCO and NCCN recommend specific genes by tumor type; when tumor testing shows certain pathogenic variants, germline testing should be offered regardless of other criteria.

Breast cancer - more strongly recommended genes: BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11, TP53.

Breast cancer - less strongly recommended genes: ATM, BARD1, CHEK2, RAD51C, RAD51D, NF1.

Colorectal cancer - more strongly recommended genes: APC, EPCAM, MLH1, MSH2, MSH6, MUTYH, NTHL1, PMS2, POLD1, POLE, BMPR1A, SMAD4, STK11, TP53.

Epithelial ovarian cancer genes: BRCA1, BRCA2, BRIP1, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51C, RAD51D.

Germline testing when tumor pathogenic variant identified

Covered when tumor testing reveals certain pathogenic variants

Tumor-detected variants requiring germline offer: If tumor testing reveals a pathogenic variant in genes such as BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C, RAD51D, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC2, VHL (and APC, PTEN, RB1, TP53 if patient <30), germline testing should be offered regardless of other germline criteria.

Discretionary germline testing after tumor findings

Covered when tumor testing reveals certain variants where offering germline testing is discretionary

Tumor-detected variants where germline testing may be offered: When tumor testing identifies pathogenic variants in genes such as ATM, BAP1, BARD1, CHEK2, DICER1, FH, FLCN, NF1, POLD1, POLE, SDHA (and CDKN2A, SMARCA4 if patient <30), offering germline testing is optional and may be considered based on clinical judgement and tumor type; a more conservative approach may limit testing to gene/tumor-specific contexts.

Individuals With a Personal History of a Primary Solid Tumor

Coverage criteria were revised; multi-gene hereditary cancer panel testing is proven and medically necessary when at least one listed criterion is met.

Personal history - revised criteria: Revised personal-history criteria include additions and clarifications such as adding malignant phyllodes tumors; modifying language regarding individuals assigned male at birth; expanding BRCA-related relative criteria to include prostate cancer; and specifying that a pathogenic variant detected in tumor tissue that has clinical implications if detected in the germline qualifies the individual for germline testing (examples listed in the policy).at least one criterion met

Individuals With No Personal History of a Primary Solid Tumor

Revised coverage criteria for individuals without a personal history of a Primary Solid Tumor; includes specified family-history criteria and other requirements.

No personal history - revised criteria: Revised no-personal-history criteria replace several relative-history items with broader neuroendocrine tumor language and clarify ovarian cancer family-history references (including fallopian tube and primary peritoneal cancer), and add new required criteria as detailed in the main policy.at least one criterion met

RNA-based panel testing performed concurrently with DNA-based hereditary cancer panels is considered to have insufficient evidence to support routine clinical use and is therefore unproven and not medically necessary for all indications. The policy notes that RNA testing may clarify some splicing variants identified by DNA testing but that existing studies are small and limited; broader adoption requires additional high-quality evidence. Similarly, genetic testing performed for the purpose of deriving a polygenic risk score (PRS) to assess hereditary cancer risk currently has insufficient evidence and is classified as unproven and not medically necessary for all indications.

Multi-gene panels that include RNA testing as a routine adjunct or panels ordered specifically to generate PRS results should not be considered standard covered services under this policy. Requests for routine concurrent RNA panel testing or for testing solely to produce a PRS are subject to denial consistent with the policy position that these uses lack established clinical utility.

Multigene hereditary cancer panels that include genes for which there is little or no evidence that a detected pathogenic variant would change medical management may be inappropriate for routine testing. The policy highlights that inclusion of low- or moderate-penetrance genes can increase findings of variants of uncertain clinical significance and may lead to unnecessary follow-up, procedures, and patient confusion.

When panels include genes of uncertain clinical actionability or low/moderate penetrance, providers are expected to document the rationale for panel selection and involve genetics expertise so results can be interpreted and applied appropriately.

Routine population-wide BRCA1/2 testing is not supported. The ACMG and USPSTF guidance cited in the policy recommend targeted risk assessment and genetic testing only for individuals whose personal or family history or ancestry suggests elevated BRCA1/2 risk. The USPSTF specifically recommends against routine genetic counseling or BRCA testing for women without personal/family history or ancestry associated with increased BRCA1/2 risk.

Per ASCO/SSO 2024 guidance, BRCA1/2 testing is recommended for individuals with newly diagnosed breast cancer aged ≤65 and for older individuals only when specific clinical qualifiers are present; this reinforces that BRCA testing should not be performed routinely in those without risk factors.

A 2023 Hayes Precision Medicine Insight examined multisyndrome (comprehensive) panels and found minimal or unclear support in the published literature and guidelines for using broad multisyndrome panel testing to guide clinical management in suspected hereditary cancer syndromes. The review identified a small number of studies and concluded that evidence of clinical benefit, comparative effectiveness versus targeted testing, and patient-important outcomes remains limited or absent.

The policy concludes that current evidence is insufficient to support routine clinical use of polygenic risk scores (PRS) for hereditary cancer risk assessment. PRS incorporate many variants of variable or unclear relevance and lack demonstrated clinical utility for hereditary cancer decision-making.

Likewise, evidence supporting routine concurrent RNA panel testing to accompany DNA hereditary cancer panels is limited; although RNA testing can sometimes clarify splicing variants, the overall quality and clinical impact of available studies are inadequate to endorse routine use.

Polygenic risk scoring for hereditary cancers is explicitly considered unproven and not medically necessary under this policy. The document states that PRS currently lack sufficient evidence to support use for hereditary cancer risk assessment and that testing performed for the purpose of PRS is not a covered or medically necessary indication.

Requests for testing where the primary rationale is PRS should be evaluated under the policy’s not-medically-necessary stance and are likely to be denied.

Multi-gene hereditary cancer panels are covered only when the individual meets the specific personal- or family-history criteria enumerated in the policy. Panels used for indications not listed as proven and medically necessary are considered unproven and not medically necessary.

The policy emphasizes that broad application of expansive panels—particularly those containing genes without established clinical management guidance—is not supported by current evidence and is not covered when ordered outside the listed clinical criteria.

The policy does not support routine testing of all individuals with breast cancer using expansive multigene panels when such testing includes genes lacking evidence to guide management. Professional guidance (ACMG, NCCN) favors targeted testing driven by personal/family history, risk-model thresholds, or therapy-directed needs rather than indiscriminate panel testing.

Ordering broader panels for all breast cancer patients without documented clinical justification or genetic expertise increases the likelihood of non-actionable findings and is discouraged.

The policy cautions against broad sequencing without a clear clinical indication or involvement of genetics expertise. Guidance from the American College of Gastroenterology and ASCO notes that large panels can increase variant uncertainty, lengthen turnaround time, and include genes with limited management data—situations in which involving providers experienced in cancer genetics is particularly important.

When multigene panels are considered, providers should document the clinical rationale, consider targeted gene analysis for the most likely syndrome when appropriate, and involve genetic counseling to support result interpretation.

Isolated ordering of tests solely to derive a polygenic risk score (PRS) is inappropriate under this policy. Similarly, routine concurrent RNA panel testing performed for every DNA-based hereditary cancer panel is not supported by the current evidence base and is considered not medically necessary when requested as a routine adjunct.

If RNA testing is requested to clarify a specific variant identified by DNA testing, documentation of that clinical question and justification should be provided; routine reflex or concurrent RNA panel testing without indication is not covered.

The policy reiterates that polygenic risk scoring (PRS) is not medically necessary for evaluation of hereditary cancer risk. Because PRS lack established clinical utility for guiding hereditary cancer management, testing performed for PRS purposes is classified as unproven and not covered.

Providers seeking coverage for tests intended to generate PRS should be aware that such requests are inconsistent with the coverage stance articulated in this policy.

Covered Indications and Scenario-Specific Rules

Covered indications — summary

Covered testing types summary: Covered germline testing includes single-gene testing, known familial mutation testing, BRCA1/2 testing per age-based criteria, and multi-gene hereditary cancer panels for individuals meeting the enumerated personal- and family-history criteria; panels are proven and medically necessary for cancers diagnosed ≤18 years.

Individuals with newly diagnosed breast cancer age <=65 — BRCA1/2 testing

ASCO/SSO 2024 recommendation for BRCA1/2 testing in breast cancer

Newly diagnosed ≤65: Offer BRCA1/2 testing to individuals 65 years of age or younger with newly diagnosed breast cancer (stage I–III or de novo stage IV).age <=65

Individuals >65 with breast cancer meeting specific qualifiers — BRCA1/2 testing

Eligibility and Documentation Requirements

For individuals without a personal history of cancer, eligibility for multigene panel testing requires demonstration of specific family-history patterns as defined in the policy. Examples include close relatives with early-onset cancers, multiple affected relatives on the same side of the family, first-degree relatives with multiple primary solid tumors, or family histories consistent with Lynch syndrome or other hereditary syndromes assessed by predictive model thresholds.

The policy requires detailed pedigree and family-history documentation (including degree of relatives and ages at diagnosis) to verify that one or more of the enumerated family-history patterns are met before coverage is approved for an unaffected individual.

Coverage for unaffected individuals is contingent on meeting one of the policy’s specified family-history patterns. Acceptable patterns include, for example, a first- or second-degree relative with colorectal or endometrial cancer diagnosed at an early age, multiple first- or second-degree relatives with Lynch-related cancers, or relatives with breast, ovarian, pancreatic, or prostate cancer meeting the enumerated counts and ages.

Providers should document the qualifying family-history node precisely (e.g., degree of relative, cancer type, age at diagnosis) in the submitted medical record or pedigree to support coverage decisions.

The policy includes alternative/duplicate family-history nodes to capture equivalent patterns of risk (for example, multiple different configurations of first- and second-degree relatives with Lynch-syndrome cancers). These alternate definitions are intended to preserve established clinical triggers for testing while providing clear documentation expectations.

When multiple family-history nodes could apply, documentation should make clear which specific node(s) the case meets to facilitate review.

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization required when indicated

Prior authorization may be required for hereditary cancer genetic testing when the member's personal and/or family history suggests a hereditary cancer susceptibility and when test results would reasonably affect medical or surgical management. Prior authorization requests should reference guideline-directed indications (for example, NCCN-, ASCO-, ACOG-, ACG- and NSGC-based criteria) and explicitly justify the clinical scenario and how the test results will influence care.

Prior authorization expectation: Genetic testing should be ordered when personal/family history suggests susceptibility and when results will influence care.
Prior authorization aligned to guideline criteria: Prior authorization must align with NCCN-defined clinically indicated testing scenarios and justify panel composition and clinical utility.

Billing Rule

Panel selection and content requirements

Billing Codes, Risk Thresholds, and Coding Guidance

Applicable proprietary codes (selection)HCPCS

0138U

BRCA1 and BRCA2 mRNA sequence analysis (List separately in addition to code for primary procedure)

Applicable CPT/HCPCS codesmixed

81162	BRCA1 and BRCA2 gene analysis; full sequence analysis and full duplication/deletion analysis
81163	BRCA1 and BRCA2 gene analysis; full sequence analysis
81164	BRCA1 and BRCA2 gene analysis; full duplication/deletion analysis
0101U	Hereditary colon cancer disorders genomic sequence analysis panel (15 genes) with mRNA analytics
0102U	Hereditary breast cancer-related disorders genomic sequence analysis panel (17 genes) with mRNA analytics
0129U	Hereditary breast cancer-related disorders genomic sequence and deletion/duplication analysis panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, TP53)
0130U	Hereditary colon cancer disorders targeted mRNA sequence analysis panel (list separately in addition to code for primary procedure)
0162U	Hereditary colon cancer (Lynch syndrome) targeted mRNA sequence analysis panel (MLH1, MSH2, MSH6, PMS2) (List separately in addition to code for primary procedure)
0238U	Oncology (Lynch syndrome) genomic DNA sequence analysis of MLH1, MSH2, MSH6, PMS2, EPCAM
0474U	Hereditary pan-cancer genomic sequence analysis panel of 88 genes

1–10 of 16

1/2

Applicable CPT Codes (added)CPT

0495U

Oncology (prostate), analysis of circulating plasma proteins and germline polygenic risk score; CPT code added to Applicable Codes as listed in Policy History

Risk model score thresholds for germline testing

Tyrer-Cuzick / BRCAPRO / Penn11 threshold (personal history)Score ≥ 2.5% for predicted probability of a BRCA1/2 pathogenic variant (used when individual has a personal history of a Primary Solid Tumor).

Tyrer-Cuzick / BRCAPRO / Penn11 threshold (no personal history)Score ≥ 5% for predicted probability of a BRCA1/2 pathogenic variant (used when individual has no personal history of a Primary Solid Tumor).

PREMM5 / MMRpro / MMRpredict threshold (personal tumor context)Score ≥ 2.5% may be used to select individuals with a personal history of CRC and/or EC for MMR gene evaluation (see LS guidance).

PREMM5 / MMRpro / MMRpredict threshold (general/no personal history)Score ≥ 5% predicted probability for an MMR gene pathogenic/likely pathogenic variant is the general threshold to prompt Lynch syndrome evaluation; PREMM5 ≥2.5% may be used in some contexts per guidance.

Not Covered / Experimental / Not Medically Necessary

Multi-gene panels for indications not listed as proven/medically necessary are not covered. The policy also specifies that RNA panel testing as a routine adjunct to DNA-based hereditary cancer panel testing and polygenic risk scoring (PRS) are not covered because evidence is insufficient to support routine clinical use.

Broad panels that include genes without established management guidance and tests ordered primarily for PRS generation or routine RNA adjunct testing should be considered non-covered and may be denied in the absence of supporting clinical justification.

The policy states that broad multigene panels containing genes without established clinical management evidence are not routinely appropriate and are not covered for indications outside the listed, guideline-consistent scenarios. Inclusion of genes with uncertain penetrance or unclear management pathways increases VUS rates and can lead to unnecessary interventions.

Ordering providers should select panels that match the clinical question and document the rationale for any broader panel requested to support coverage consideration.

Population-wide routine BRCA testing or BRCA testing in individuals without a personal/family history or ancestry risk consistent with guideline screening is not covered. The USPSTF and ACMG guidance cited in the policy recommend targeted screening and counseling rather than universal BRCA testing.

Requests for routine BRCA testing outside of the documented criteria should be expected to be denied under the policy’s not-covered provisions.

The Hayes 2023 review found minimal or unclear support for multisyndrome panel testing to inform clinical management in some suspected hereditary cancer syndromes; based on this review and similar evidence gaps, use of broad multisyndrome panels in contexts not specifically supported by guidelines is not covered.

Background, Definitions, and Evidence Context

Hereditary cancer susceptibility accounts for an estimated 5–10% of cancers overall. Hereditary syndromes typically show earlier onset and autosomal dominant inheritance patterns; thorough multigenerational family history taking focused on ages at diagnosis and tumor types is central to risk assessment and to determining appropriate testing.

The policy underscores that germline testing is most valuable when it can be interpreted and applied in clinical management; therefore, testing should be targeted to persons meeting established clinical criteria.

BRCA‑Related Cancers

DefinitionBRCA‑Related Cancers include breast cancer; ovarian/fallopian tube/primary peritoneal cancer; pancreatic cancer; and prostate cancer.

Source guidanceDefinition aligned with NCCN Genetic/Familial High‑Risk Assessment guidance cited in the policy.

Clinical relevanceThese cancer types are specifically referenced when determining BRCA‑associated testing indications and family‑history triggers.

Policy Revision History and Changes

2026-04-01template_update

Template update removed Louisiana-specific content.

2025-06-01coverage_criteria_revision

Revised coverage criteria for individuals with a personal history of a Primary Solid Tumor, including added malignant phyllodes tumor criterion, broadened neuroendocrine tumor language, clarified ovarian cancer wording, modified male-assigned-at-birth language, and specified tumor-detected genes with germline implications.

2025-06-01coverage_criteria_revision

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer

Policy CodePolicy CS049.Z

Change TypeCoverage criteria revisedadded exclusions

Effective DateJun 1, 2025

Next Review Date

Key ActionDocument pedigree, family history, and genetic counseling and verify prior authorization/benefit terms before submitting testing requests.

SourceLink

On This Page

Pancreatic cancer-specific clinically indicated criteria: Indication: personal history of pancreatic adenocarcinoma or clinical suspicion; germline testing using comprehensive panels is recommended for any confirmed pancreatic adenocarcinoma.

Prostate cancer-specific clinically indicated criteria: Indication: metastatic or high/very-high risk prostate cancer or family/ancestry features (close relatives with early breast/ovarian/pancreatic/metastatic prostate cancer, multiple relatives on same side, Ashkenazi ancestry); panels should include at minimum BRCA1/2, ATM, PALB2, CHEK2, HOXB13, and mismatch-repair genes where indicated.

Colorectal/Endometrial (Lynch) clinically indicated criteria: Indication: CRC or EC diagnosed <50 years, tumor dMMR/MSI-high, multiple LS-related primaries, family history meeting defined counts/ages, PREMM5/MMRpro thresholds, or ≥10 cumulative adenomas; germline MGPT should include minimum CRC/LS genes per NCCN.

Prostate cancer recommended genes: BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, PMS2.

Pancreatic adenocarcinoma genes: ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53.

ASCO/SSO guidance for BRCA1/2 testing in individuals >65 with qualifying features

>65 with qualifiers: Offer BRCA1/2 testing to individuals >65 with breast cancer if they are PARP inhibitor candidates, have triple-negative disease, have personal/family history suggestive of a pathogenic variant, are assigned male at birth, or are of Ashkenazi/founder-population ancestry.

All women with epithelial ovarian cancer — germline testing

ASCO guideline for epithelial ovarian cancer

All women with epithelial ovarian cancer: All individuals with epithelial ovarian, fallopian tube, or primary peritoneal cancer should undergo germline testing for BRCA1/2 and other ovarian susceptibility genes; if germline BRCA1/2 testing is negative, somatic tumor testing for BRCA1/2 should be performed.

Germline genetic testing for individuals meeting guideline criteria

Germline genetic testing is covered for individuals meeting established society criteria for multiple cancer types

NCCN/ASCO indicated cancers: Germline testing is covered for individuals meeting NCCN/ASCO/other society criteria for hereditary breast, ovarian, pancreatic, colorectal, endometrial, gastric, and prostate cancer — including testing to guide therapy (e.g., PARP inhibitor eligibility) and to inform family risk assessment.

Evaluation for Lynch syndrome — indications

Evaluation for Lynch syndrome is indicated when family history, personal cancer history, tumor features, or risk-model thresholds are met

LS evaluation: Indications include known family LS pathogenic variant; CRC or EC diagnosed ≤49 years; synchronous/metachronous LS-related cancers; first- or second-degree relative with LS-related cancer ≤49; two or more first- or second-degree relatives with LS-related cancers; predictive model risk ≥ thresholds (PREMM5/MMRpro/MMRpredict); tumor dMMR/MSI-high or absent MMR protein staining; or tumor-detected P/LP variant with germline implications. PREMM5 thresholds of ≥2.5% may be used in certain contexts; general predictive-model threshold often cited ≥5%.

Adenomatous polyposis genetic testing

Adenomatous polyposis genetic testing indications

Adenomatous polyposis indications: Testing indicated for individuals with ≥20 cumulative adenomas; family history of known pathogenic variant in adenomatous polyposis genes; multifocal/bilateral CHRPE; cribriform-morular variant of papillary thyroid cancer; or family history of polyposis when affected family members are unwilling/unable to test. Consider testing for 10–19 adenomas and other related features; tumor-detected APC variants in cancer should prompt germline consideration in appropriate contexts.

Hamartomatous polyposis syndrome MGPT

Hamartomatous polyposis syndrome MGPT indications

Hamartomatous polyposis MGPT: Perform genetic evaluation and MGPT for individuals with two or more lifetime hamartomatous polyps; family history of hamartomatous polyps or associated cancer in first/second-degree relatives; two or more Peutz–Jeghers polyps; Peutz–Jeghers features plus family history or mucocutaneous pigmentation; five or more juvenile colonic polyps; or juvenile polyps with an affected first-degree relative.

MGPT for pancreatic, PPGL, kidney, and other solid tumors

MGPT for other solid tumors when guideline- or study-supported or when results would impact management

Other solid tumors (pancreas, PPGL, kidney, etc.): Germline MGPT is indicated for individuals with pancreatic cancer, pheochromocytoma/paraganglioma (PPGL), kidney cancer, or other solid tumors when recommended by guidelines or studies, or when germline results would impact treatment, surveillance, or family members; published studies report clinically relevant PGV yields in these populations.

Germline testing for prostate cancer

Prostate cancer germline testing guidance

Prostate cancer panels: Offer germline multigene testing for prostate cancer when criteria are met and when results could impact therapy, risk management, or family members; include at minimum BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2 per NCCN.

Germline comprehensive panels for pancreatic adenocarcinoma

Pancreatic adenocarcinoma testing recommendation

Pancreatic adenocarcinoma MGPT: Germline comprehensive panels are recommended for any individual with confirmed pancreatic adenocarcinoma or clinical suspicion for hereditary susceptibility; genetic counseling is recommended for mutation-positive individuals and those with family history.

Hereditary endocrine neoplasia testing

Hereditary endocrine neoplasia testing indications

Endocrine neoplasia testing: Genetic testing is indicated for hereditary endocrine neoplasia syndromes when clinical criteria are met (e.g., adrenocortical carcinoma, pheochromocytoma/paraganglioma, parathyroid adenoma or hyperparathyroidism <30 years, clinical suspicion for MEN2/MEN1), and multigene panels may be efficient due to syndrome overlap.

MGPT coverage for individuals with personal history

Testing with a Multi-Gene hereditary cancer Panel is proven and medically necessary when at least one listed criterion is met for individuals with a personal history of a Primary Solid Tumor.

MGPT coverage for personal history: Multi-Gene hereditary cancer Panel testing is proven and medically necessary for individuals with a personal history of a Primary Solid Tumor when at least one of the specified personal- or family-history criteria in the policy is met (see personal-history criteria group).

BRCA1/2 testing for breast cancer diagnosed ≤65

BRCA1/2 testing proven and medically necessary for specified breast cancer ages

BRCA1/2 testing age ≤65: BRCA1/2 gene testing is proven and medically necessary for individuals with a personal history of breast cancer diagnosed at age 65 or younger.age <=65

Many of the eligibility nodes rely on first-degree relative patterns—such as a first-degree relative with two or more different primary solid tumors or a first-degree relative with early-onset breast, ovarian, pancreatic, or prostate cancer. The policy requires that these relationships and ages be specified in the pedigree or medical record.

Accurate notation of relative type (first vs second degree), ages at diagnosis, and tumor types is essential for determining whether an unaffected person meets coverage criteria.

Additional top-level family-history eligibility nodes include criteria tied to Lynch syndrome (e.g., multiple relatives with LS-related cancers, at least one relative diagnosed at <50 years) and nodes reflecting family histories that meet polyposis thresholds or include multiple adenomas.

These nodes are meant to capture the major hereditary colorectal and endometrial cancer family-history patterns that trigger germline testing under established guideline-based thresholds.

Other top-level eligibility nodes encompass family histories compatible with adenomatous polyposis (for example, relatives meeting polyposis diagnostic criteria) and family histories with multiple affected relatives across related tumor types that suggest established hereditary syndromes.

When these nodes are invoked for coverage decisions, providers should include documentation such as colonoscopy reports, pathology, or detailed family pedigrees as appropriate.

The policy history documents substantive revisions to eligibility criteria. Changes include addition of specific criterion items (for example, personal history of malignant phyllodes tumors) and replacement or clarification of relative-history wording (for example, expanding prostate cancer language in BRCA-relative definitions and replacing paraganglioma/pheochromocytoma references with broader neuroendocrine tumor language).

These revisions reflect updates to align the policy with guideline changes and to clarify which family-history patterns meet coverage thresholds for unaffected individuals.

Known familial pathogenic variants and targeted single-gene testing remain covered when clinically appropriate. The policy supports testing of a specific known familial mutation (cascade testing) and single-gene analysis when a family’s known variant or the clinical presentation indicates a particular gene is most likely implicated.

Additionally, tumor testing results (for example, tumor-detected pathogenic variants in genes with germline implications or tumor dMMR/MSI-high findings) may prompt germline testing, and such scenarios are recognized as coverage triggers when the gene implicated has clinical implications if present in the germline.

The policy reiterates that when a specific familial pathogenic variant is known, testing the appropriate family members for that known variant (single-site or targeted testing) is covered. This approach is the preferred, cost-effective strategy when an affected relative’s positive result is already established.

Tumor genomic findings that suggest a germline origin for a variant also justify offering germline testing and are considered in coverage determinations when adequately documented.

Coverage for single-gene testing for a known familial mutation is reiterated: when a familial P/LP variant is identified, targeted testing of at-risk relatives is covered and should be performed as the initial approach where applicable.

Testing should be coordinated with appropriate documentation of the familial variant and relationship to the proband to support coverage.

The policy emphasizes that when tumor testing identifies variants that could represent germline findings, germline testing should be considered and is covered when the implicated gene has established germline implications and when documentation supports the clinical rationale.

Documentation of the tumor result and its clinical implications, along with counseling and a plan for management if a germline variant is confirmed, should be included in the request for coverage.

Additional eligibility nodes include family-history configurations tied to Lynch syndrome and predictive-model risk thresholds (PREMM5/MMRpro/MMRpredict). The policy incorporates guidance that model-based thresholds (generally ≥5%) and certain PREMM5 scores (≥2.5% in some contexts) can be used to select individuals for MMR gene testing.

Providers should document predictive model scores and the clinical context when relying on these thresholds to support coverage.

The policy notes that individuals with tumor dMMR by PCR, NGS, or IHC, or with tumor findings suggestive of a germline MMR pathogenic variant, meet criteria for germline evaluation for Lynch syndrome. Such tumor-based evidence can be used to justify germline panel testing when appropriately documented.

When tumor testing is used as a trigger, the tumor assay result and interpretation should be supplied to support the coverage decision.

Policy revisions clarified that BRCA1/2 testing and MGPT coverage criteria were updated to reflect current practice and guideline recommendations. These updates also added tumor-based triggers and specified gene lists that have germline implications when identified in tumor tissue.

The history notes these clarifications to ensure that coverage aligns with genes that would change clinical management or have established germline implications.

Multigene panels must be limited to indications where panel testing is expected to provide clinical benefit. Panels that do not meet the policy's specified indications are considered unproven and not medically necessary. For CRC- or EC-related panels, ensure the panel includes at minimum the CRC- or EC-related genes specified by NCCN; broader panels require documentation of rationale tied to phenotype, age, and family history.

Panel restriction: Multi-gene panels are limited to specified indications; otherwise unproven and not medically necessary.
Panel gene content requirement: For CRC panels include at minimum APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM, BMPR1A, SMAD4, PTEN, STK11, TP53; for EC include MLH1, MSH2, MSH6, PMS2, EPCAM, PTEN, POLD1, POLE, BRCA1/2.
Laboratory/panel selection risk: Commercially available panels differ substantially in gene content, number of genes, analytic methods, and turnaround time — choice of laboratory/test panel is critical.

Denial Risk

Concurrent RNA testing — limited evidence and potential denial

Concurrent RNA panel testing with DNA-based hereditary cancer panels is considered investigational for routine use given limited and low-quality evidence. Prior authorization may be required for concurrent RNA testing and such requests may be denied; if submitted, provide explicit clinical rationale and supporting evidence for why RNA testing is necessary at the time of DNA testing.

Prior auth for concurrent RNA testing: Routine concurrent RNA panel testing has insufficient evidence; prior authorization may be required and denials are possible.
RNA panel testing denial risk: Requests for routine concurrent RNA panels are at risk for denial without strong clinical justification and supporting documentation.

Note

Verify benefit and prior authorization requirements

Verify member benefit terms and applicable plan rules, including federal, state, or contractual requirements, before ordering or authorizing testing. Use any available prior authorization tools (including third-party tools such as InterQual) and the member’s specific plan to determine coverage, medical necessity, and any step-therapy or sequencing requirements.

Verify prior authorization and benefit terms: Coverage is determined by federal, state, or contractual plan requirements; check plan-specific prior authorization tools and criteria.
Unit-specific rules: UnitedHealthcare may use third-party tools (e.g., InterQual) to assist administration; always confirm the member’s plan details.

Denial Risk

Polygenic risk scoring is not covered

Testing requested for the purpose of polygenic risk scoring is considered unproven and not medically necessary. Requests for polygenic risk scores should not be approved unless there is clear, plan-supported evidence of clinical utility for the individual member.

Polygenic risk scoring—denial risk: Genetic testing solely to generate polygenic risk scores is unproven and may be denied.

Documentation Required

Pedigree and family history documentation required

Provide contemporaneous, detailed personal and family history documentation with all testing requests. A pedigree drawing/diagram using standardized nomenclature must be included in the medical record and submitted with the prior authorization request. Document degrees of relationship, ages at diagnosis, tumor types, and relevant non-cancer clinical features.

Pedigree requirement: Personal and family history documentation should be a pedigree drawing/diagram using standardized nomenclature.
Family history and risk assessment: Include detailed family history (degrees and ages at diagnosis) and hereditary cancer risk assessment or referral.
Family history documentation: Comprehensive family history must be recorded for all individuals with cancer.

Documentation Required

Required clinical documentation and risk of insufficient records

Clinical documentation submitted with the request must include: a thorough personal and family history (pedigree), results of any prior genetic or tumor testing, the specific clinical question or management decision the test will inform, documentation of genetic counseling or referral, and any risk model scores (e.g., PREMM5) if used. Lack of contemporaneous records or pedigree may result in inability to demonstrate criteria are met and denial of the request.

Required clinical documentation: Personal and family history, prior genetic/tumor testing results, rationale for panel choice tied to phenotype/management, and documentation of genetic counseling or referral.
Documentation risk: Absence of contemporaneous medical records/pedigree may lead to inability to demonstrate that member meets criteria.

Documentation Required

Genetic counseling and provider expertise

Genetic counseling is strongly recommended (and may be required by some plans) prior to testing and after results disclosure. Testing should be ordered or interpreted by providers with expertise in cancer genetics when possible. For results that identify pathogenic or likely pathogenic variants, coordinate cascade testing and appropriate management discussions for family members.

Genetic counseling documentation: Include notes documenting pre-test counseling or involvement of providers with expertise in cancer genetics.
Provider expertise: Multigene testing is ideally offered with professional genetic expertise; counseling facilitates informed consent and interpretation.

Step Therapy

Sequencing, step-therapy, and pancreatic cancer testing approach

When multiple testing strategies are clinically reasonable, consider targeted/smaller panels first if rapid results are needed to guide immediate treatment; larger or broader panels can be ordered subsequently if initial testing is non-diagnostic or additional information is required. For pancreatic adenocarcinoma, follow NCCN guidance and use comprehensive germline panels — no step-therapy sequencing is required for pancreatic cancer testing.

Step therapy / sequencing considerations: Prefer targeted gene analysis for the syndrome most likely to explain the presentation; avoid broad panels without justification.
Sequential panel strategy: Smaller panels may be used initially for rapid treatment decisions with larger panels ordered later if indicated.
Pancreatic cancer testing approach: For pancreatic adenocarcinoma, use comprehensive germline panels per NCCN; no step-therapy requirement.

PREMM5/MMR risk score

General PREMM5/MMRpro thresholdPredictive model risk ≥ 5% predicted probability of a germline MMR pathogenic/likely pathogenic variant (e.g., PREMM5, MMRpro, MMRpredict).

PREMM5 lower-threshold optionIndividuals with a personal history of CRC and/or EC with a PREMM5 score ≥ 2.5% should be considered for multigene panel testing or MMR evaluation; PREMM5 ≥2.5% may be used for some individuals without personal history when clinical judgment applied.

Tumor dMMR as alternative triggerPersonal history of a tumor with dMMR (MSI‑high or abnormal MMR IHC) is an indication for LS evaluation independent of model score.

Age for LS consideration

Age trigger for LS considerationColorectal cancer (CRC) or endometrial cancer (EC) diagnosed at age 49 years or younger (≤49) should prompt Lynch syndrome evaluation and testing.

Synchronous/metachronous tumorsAny age with synchronous or metachronous LS‑related cancers should prompt LS testing regardless of age at first diagnosis.

Relative age criteriaPresence of first‑ or second‑degree relatives with LS‑related cancers diagnosed ≤49 years strengthens indication for testing.

Age threshold for BRCA1/2 testing

BRCA1/2 testing age thresholdBRCA1/2 gene testing is proven and medically necessary for individuals with a personal history of breast cancer diagnosed at age 65 years or younger.

ASCO/SSO recommendation contextASCO/SSO 2024 recommends offering BRCA1/2 testing to individuals with newly diagnosed breast cancer age ≤65 (stage I–III or de novo stage IV).

Testing >65 with qualifiersIndividuals older than 65 may be offered BRCA1/2 testing if eligible by PARP candidacy, triple‑negative status, suggestive personal/family history, male breast cancer, or founder‑population ancestry.

NCCN and ASCO recommendations for specific tumor types (for example, pancreatic adenocarcinoma) remain endorsed where guideline-based testing is indicated; however, indiscriminate multisyndrome panel use outside those contexts is not covered.

Routine clinical use of polygenic risk scores and routine concurrent RNA panel testing with DNA hereditary cancer panels are not covered because current evidence is insufficient to demonstrate clinical utility. The policy explicitly states these modalities are unproven and not medically necessary for all indications.

Coverage requests reliant on PRS results or requesting routine RNA panels alongside all germline panels should be expected to be denied.

Genetic testing performed specifically for the purpose of generating a polygenic risk score for hereditary cancers is classified as unproven and not medically necessary and therefore not covered under this policy. The policy history explicitly added language to reflect this stance.

Providers should not submit testing requests premised solely on PRS generation if seeking coverage under the standard criteria described in this policy.

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

Panel content notePolicy cautions that many commercial panels include low‑ or moderate‑risk genes that may lack evidence to change management and can increase VUS rates.

Test typesMGPT may include sequencing and large deletion/duplication analysis as part of comprehensive germline testing when indicated.

P/LP (Pathogenic / Likely Pathogenic) variant

DefinitionP/LP = pathogenic or likely pathogenic variant — a genetic alteration classified as disease‑causing or likely disease‑causing.

Clinical implicationIdentification of a P/LP variant in an established cancer susceptibility gene guides management and cascade testing of relatives.

Testing methodsWhen testing is indicated, include full gene sequencing and deletion/duplication analysis per ACMG recommendations to detect P/LP variants.

Variant of Uncertain Significance (VUS)

DefinitionVUS = Variant of Uncertain Significance — a genetic variant whose clinical significance is unclear and should not be used to guide medical management.

Management caveatPolicy and ASCO/ACMG statements emphasize that VUS results should not change clinical management and require genetic counseling for interpretation.

Potential outcomesVUS findings may prompt additional follow‑up or reclassification over time; they do not constitute a P/LP result for cascade testing decisions.

Lynch syndrome

DefinitionLynch syndrome (LS) = condition used only when individuals have germline heterozygous pathogenic/likely pathogenic variants in mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 or 3' terminal deletions of EPCAM.

Gene setLS diagnosis relies on identification of germline P/LP variants in MLH1, MSH2, MSH6, PMS2 or EPCAM deletions.

Clinical useThe policy specifies using the term ‘Lynch syndrome’ only after germline confirmation in these genes.

VUS — clinical caveat

Interpretation guidanceVUS interpretation and potential reclassification require genetics expertise; VUS should not be used for cascade testing.

Relation to panelsMulti‑gene panels increase the likelihood of detecting VUS, underscoring need for pre/post‑test counseling.

Lynch syndrome (LS) — definition

Lynch syndrome (LS) definition — emphasisCondition defined by germline heterozygous P/LP variants in MMR genes MLH1, MSH2, MSH6, PMS2 or 3' terminal deletions of EPCAM; policy reiterates this diagnostic criterion.

Terminology cautionPolicy advises reserving the LS label for confirmed germline findings rather than tumor‑only results.

Genetic implicationsGermline LS diagnosis carries implications for surveillance and testing of relatives per CGA‑IGC/NSGC guidance.

LS‑related cancers

LS‑related cancers (examples)Colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, brain (usually glioblastoma), biliary tract, small intestine, and sebaceous tumors (adenomas/carcinomas) among others.

Clinical noteThese tumor types are listed as Lynch syndrome–associated and are used in family‑history and testing criteria to identify individuals for LS evaluation.

Policy usagePresence of these cancers in probands or relatives (with specified counts/ages) triggers consideration of MMR gene testing or MGPT including MMR genes.

Polygenic Risk Score (PRS)

DefinitionPolygenic Risk Score (PRS) = an evaluation of risk based on the combined effect of many genetic variants; current evidence is insufficient to support use of PRS for hereditary cancer risk assessment.

Policy stancePRS are considered to have insufficient evidence for clinical use in hereditary cancer risk assessment and are classified as unproven/not medically necessary for this purpose.

ImplicationRequests for testing to generate PRS for hereditary cancer are subject to denial per the policy.

RNA panel testing (concurrent)

DefinitionConcurrent RNA panel testing = RNA‑based assays performed alongside DNA multigene hereditary cancer panels to clarify splicing variants or resolve inconclusive DNA findings.

Evidence stanceThere is insufficient evidence to support routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels; routine use is not supported by current data.

Clinical noteRNA testing may clarify certain variants and can increase diagnostic yield in select cases, but policy requires justification and may deny routine concurrent RNA testing.

Primary Solid Tumor

DefinitionPrimary Solid Tumor — term used in the policy to denote non‑skin primary solid malignancies for which multi‑gene hereditary cancer panel testing criteria are applied.

Scope notePolicy explicitly excludes basal or squamous cell skin cancer from Primary Solid Tumor criteria.

UsagePresence of a Primary Solid Tumor is a key determinant for applying personal‑history testing criteria in the policy.

Neuroendocrine tumor (examples)

Examples of neuroendocrine tumorsPolicy examples include adrenocortical carcinoma, paraganglioma, and pheochromocytoma as neuroendocrine tumors relevant to testing criteria.

Revised languagePolicy revisions replaced paraganglioma/pheochromocytoma references with broader ‘neuroendocrine tumor’ language (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma).

Testing implicationPersonal or family history of listed neuroendocrine tumors can meet criteria for MGPT per the policy lists.

Revised coverage criteria for individuals with no personal history of a Primary Solid Tumor, including replacing first-degree relative paraganglioma/pheochromocytoma language with broader neuroendocrine tumor language and clarifying ovarian/fallopian tube/primary peritoneal cancer family-history language.

2025-06-01added_policy_language

Added language that genetic testing for the purpose of polygenic risk scoring for hereditary cancers is unproven and not medically necessary for all indications.

2025-06-01coding_update

Added CPT code 0495U to Applicable Codes.

2026-04-01policy_history_entryLatest

Multiple policy history entries summarizing the above substantive changes and administrative updates as recorded in Policy History.

Material changes summarized in the policy history include revision of coverage criteria for Multi-Gene hereditary cancer Panel testing for individuals with and without a personal history of a Primary Solid Tumor, addition of specific criterion items (for example, malignant phyllodes tumors), clarification of family-history language (for example, replacing paraganglioma/pheochromocytoma references with broader neuroendocrine tumor language), and addition of language declaring genetic testing for polygenic risk scoring as unproven and not medically necessary.

The policy history also notes that CPT code 0495U was added to the list of applicable codes and that a template update removed Louisiana-specific content.