DraftUnitedHealthcarePolicy CS049NE.E

Genetic Testing for Hereditary Cancer (Nebraska)

Policy governing coverage criteria for genetic testing for hereditary cancer for UnitedHealthcare members in Nebraska; defines when single-gene, multigene panel, RNA, polygenic risk score, and whole-exome/genome testing are considered medically necessary or not.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer (Nebraska)

Policy CodePolicy CS049NE.E

Change TypeRevisions to coverage criteriaadded WES/WGS languagecode updates

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionWhen ordering germline multigene panel testing, include rationale for panel choice and document pretest genetic counseling or a plan for counseling.

SourceLink

POLICY UPDATE CHANGES

Revised coverage criteria for genetic testing with a Multigene hereditary cancer Panel for individuals with a personal history of a Primary Solid Tumor, adding specific renal cell carcinoma and serous tubal intraepithelial carcinoma criteria.

Replaced criterion requiring a PENN11 score with requirement for a CanRisk score when assessing 2.5% BRCA1/2 risk (alongside Tyrer-Cuzick or BRCAPRO).

Added language that whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes or risk is unproven and not medically necessary.

Revised coverage criteria for individuals with no personal history of a Primary Solid Tumor, adding family-history requirement of two or more first- or second-degree relatives on the same side with renal cell carcinoma.

Removed definition of High Penetrance Breast Cancer Susceptibility Genes and Penetrance.

Updated multiple definitions including Age Guidelines, BRCA-Related Cancers, Gleason Scoring, Lynch Syndrome-Associated Cancer, Ovarian Cancer, Personal and Family History Documentation, PREMM5, and Primary Solid Tumor.

Removed CPT codes 0131U, 0132U, and 0135U from applicable codes for Multigene Panel.

Added CPT codes 0212U, 0213U, 0214U, 0215U, 0265U, 0266U, 81415, 81416, 81417, 81425, 81426, and 81427 for Whole Exome and Whole Genome Sequencing.

5+ genes

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Definition threshold for a Multigene Panel

<=65BRCA testing age

2.5%/5%Risk score thresholds

Not coveredRNA panels

multipleWES/WGS codes added

Coverage Criteria and Rationale

Medical necessity criteria and exclusions

Covered when criteria below are met for individuals with or without a personal history of a Primary Solid Tumor

Pretest counseling: Pretest genetic counseling is strongly recommended to inform persons being tested about the advantages and limitations of the test.

recommended, not strictly required per text

Individuals with personal history of Primary Solid Tumor - BRCA tier: BRCA1/2 gene testing is proven and medically necessary for individuals with Breast Cancer diagnosed at age 65 years or younger.<=65 years

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Individuals with personal history of Primary Solid Tumor - Multigene panel criteria: Multigene hereditary cancer panel is medically necessary when an individual with a Primary Solid Tumor (excluding basal or squamous cell skin cancer) meets at least one specified personal history criterion, including but not limited to: breast cancer ≤50 years, metastatic breast cancer, multiple primary breast cancers, triple-negative breast cancer, lobular breast cancer with diffuse gastric cancer history, Ashkenazi Jewish ancestry, male breast cancer, unknown/limited family history, BRCA-related family cancers, ovarian cancer (including fallopian tube, primary peritoneal, sex‑cord tumors with annular tubules, hypercalcemic-type small cell carcinoma of the ovary), serous tubal intraepithelial carcinoma, pancreatic cancer, metastatic prostate cancer, Lynch syndrome–associated cancer, neuroendocrine tumor, malignant phyllodes tumor, renal cell carcinoma meeting renal criteria (diagnosed ≤46 years, bilateral/multifocal, first- or second-degree relative with RCC, personal/family history of mesothelioma or uveal melanoma), or at least two different primary solid tumors.at least one listed criterion

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Personal history + family history: Multigene panel is covered if the individual has a personal Primary Solid Tumor and a family history meeting specified patterns, such as: at least one close blood relative with a Lynch-associated cancer; at least one close blood relative diagnosed ≤40 years with a Primary Solid Tumor; or at least two close blood relatives (in addition to the proband) on the same side with Primary Solid Tumors.at least one listed family criterion

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Personal history + tumor/tumor-testing triggers: Coverage is warranted when personal tumor testing reveals a pathogenic variant with germline implications (examples listed), when tumor testing shows MSI‑high or loss of MMR protein expression, when renal tumors have specified histologic features associated with hereditary RCC, or when risk-model scores meet thresholds (Tyrer‑Cuzick, BRCAPRO, or CanRisk ≥2.5% for BRCA1/2; PREMM5/MMRpro/MMRpredict ≥2.5% for Lynch in some contexts).as listed

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Individuals with no personal history (unaffected) coverage: Multigene panel or BRCA1/2 testing is medically necessary for unaffected individuals when family history meets specified criteria, for example: a first-degree relative with two or more different primary solid tumors, a first- or second-degree relative with early-onset breast cancer (≤50), TNBC, male breast cancer, metastatic prostate, ovarian, or pancreatic cancer; two or more relatives with Lynch cancers; two or more first- or second-degree relatives on same side with renal cell carcinoma; Ashkenazi Jewish ancestry plus a BRCA-related relative; three close blood relatives on same side with primary solid tumors; or family member meeting polyposis criteria who is unwilling or unable to test.at least one listed family criterion

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Pediatric oncology: Multigene hereditary cancer panels are proven and medically necessary for individuals diagnosed with cancer at age 18 years or younger.<=18 years

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Not medically necessary statements: Multigene hereditary cancer panels, RNA panel testing for hereditary cancers, polygenic risk scoring for hereditary cancers, and whole‑exome/whole‑genome sequencing for the purpose of identifying hereditary cancer syndromes or risk are unproven and not medically necessary for indications not otherwise specified as covered.N/A

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Narrative coverage considerations

Clinical indications and considerations described in narrative form

General indications: Testing is generally recommended when (1) there is a personal or family history consistent with hereditary cancer susceptibility, (2) the test can be adequately interpreted, and (3) the results can be used to diagnose or influence medical management of the individual or at‑risk family members.

From Description of Services and Robson et al., 2015 summary guidance

BRCA testing modalities: BRCA1/BRCA2 testing options include targeted founder-variant analysis (e.g., Ashkenazi Jewish ancestry), full sequence analysis, and duplication/deletion analysis; multigene panels are an alternative when broader testing is indicated.

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Multigene panels vs stepwise testing: Multigene panels may be efficient when multiple syndromes are suspected and can increase detection of P/LP variants versus stepwise testing, but panels can include low/moderate‑penetrance genes with uncertain management implications; panel selection should consider family history, phenotype, clinical utility, and availability of genetic counseling.

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Clinically Indicated Testing

Testing is clinically indicated when one or more of the following general or syndrome-specific criteria are met:

General clinically indicated criteria: A patient meets any of: a blood relative with a known pathogenic/likely pathogenic variant; prior limited testing negative but patient meets criteria and desires multigene testing; a tumor genomic finding suggests germline implication; testing will aid systemic therapy or surgical decisions; or meets testing criteria for Li‑Fraumeni, Cowden/PTEN hamartoma tumor syndrome, or Lynch syndrome.

NCCN general criteria

Breast cancer-specific indications: Patient with personal history of breast cancer diagnosed ≤50 years; breast cancer at any age when testing informs treatment (e.g., PARP inhibitors, adjuvant olaparib); pathology features such as triple‑negative disease, multiple primaries, lobular histology with diffuse gastric cancer family history, male breast cancer; Ashkenazi Jewish ancestry; close relative with early breast or related cancers; unaffected patient with a first‑ or second‑degree relative meeting criteria; or >5% probability of BRCA1/2 P/LP variant by models.

NCCN breast criteria

Ovarian cancer-specific indications: Any patient with epithelial ovarian, fallopian tube, or peritoneal cancer at any age; nonepithelial ovarian cancer types at any age; unaffected patients with a first‑ or second‑degree relative with epithelial ovarian cancer; or >5% BRCA1/2 probability by models.

May Be Considered

Testing may be considered when the benefit is less certain but counseling and management plans are available:

Breast cancer - may be considered: Personal history of breast cancer at age ≤65 who do not meet stricter criteria; individuals with a 2.5%–5% BRCA1/2 probability by models (Tyrer‑Cuzick, BRCAPRO, CanRisk); personal history plus relatives with intermediate‑risk prostate cancer with specific histology; malignant phyllodes tumors.2.5% to 5% probability in some scenarios

NCCN guidance

Ashkenazi or special populations: Testing may be considered in patients of Ashkenazi Jewish ancestry without other risk factors and in selected cases such as serous endometrial cancer.

NCCN and society statements

Low Probability

Low probability scenarios: Breast cancer diagnosed >65 years in individuals assigned female at birth with no relevant family history; localized prostate cancer with Gleason <7 and no relevant family history — probability <2.5% of identifying high‑penetrance genes.<2.5%

NCCN low‑probability note

Lynch Syndrome testing

Covered when ANY of the following Lynch syndrome (LS) evaluation criteria are met

LS evaluation criteria: 1) Known family LS pathogenic/likely pathogenic variant; 2) Personal history of LS‑related cancer with age <50, tumor dMMR (MSI‑high or abnormal IHC), synchronous/metachronous LS cancers, or first‑/second‑degree relative with LS‑related cancer; 3) Family history permutations (e.g., ≥2 first‑ or second‑degree relatives with LS cancers, including early‑onset patterns or ≥3 relatives); 4) Predictive model score ≥5% for MMR gene PV (with option to use ≥2.5% in some personal history contexts); 5) Personal tumor dMMR at any age; 6) Personal history of tumor P/LP variant on tumor testing with germline implications.

See detailed list in source chunks for specific relative/age permutations and PREMM5 guidance.

Adenomatous polyposis testing

Covered when ANY of the following adenomatous polyposis criteria are met

Adenomatous polyposis criteria: 1) Personal history of ≥20 cumulative adenomas; 2) Family history of a known pathogenic variant in an adenomatous polyposis gene; 3) Multifocal/bilateral congenital hypertrophy of the retinal pigment epithelium; 4) Personal history of cribriform‑morular variant of papillary thyroid cancer; 5) Family history of polyposis when family is unwilling/unable to undergo testing. Consider testing in patients with 10–19 adenomas or related tumors per guidance.

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Hamartomatous polyposis testing

Covered when MGPT is indicated for hamartomatous polyposis and related syndromes

Hamartomatous polyposis criteria: Genetic evaluation and MGPT when indicated for: two or more lifetime hamartomatous polyps; family history of hamartomatous polyps; cancer associated with hamartomatous polyposis in first‑ or second‑degree relatives; specific criteria for Peutz‑Jeghers (e.g., ≥2 histologically confirmed Peutz‑Jeghers polyps or characteristic mucocutaneous pigmentation with family history) and juvenile polyposis (e.g., five or more juvenile polyps or relevant family history).

USMSTF recommendations (strong, low quality)

Other cancers / multisyndrome testing

Consider MGPT for other tumors or when multisyndrome suspicion exists

Other cancers/multisyndrome testing: Evidence supports MGPT in pheochromocytoma/paraganglioma (high diagnostic yield) and in pancreatic and other solid tumors where MGPT may identify actionable findings and inform treatment and family counseling. Multigene testing may be preferred when overlapping syndromes are suspected or when tumor findings suggest germline risk.

Study and guideline summaries; consider individualized choice of panel and counseling

Guideline-based indications for germline multigene testing

Covered when ANY of the following guideline-based indications are met (per ASCO and NCCN summaries in this section):

ASCO general: All patients with cancer should have a comprehensive family history; germline testing using a multigene panel should be offered when indicated and panels should include at minimum the more strongly recommended genes for the patient based on personal/family history.

ASCO 2024 recommendations

Tumor to germline: When tumor testing reveals a pathogenic variant in designated genes, germline testing should be offered; tumor PVs may prompt germline testing in specified genes and ages.

ASCO: tumor PV prompting germline testing

Prostate cancer: Germline testing should be considered in prostate cancer candidates when results could impact treatment or trials; panels should include BRCA1/2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, PMS2.

NCCN Prostate v2.2026

Evidence-based coverage statements (narrative)

Summary of evidence-based stances from document excerpts

PRS use: Polygenic risk scores (PRS) have limited clinical utility alone; ACMG does not support routine clinical implementation unless limitations are understood and management is evidence‑based. PRS may improve predictive performance when combined with clinical variables but should not be used in isolation to direct care.

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RNA panel testing with BRCA/multigene panels: Evidence is insufficient to support routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels; RNA testing may clarify some variants and modestly increase diagnostic yield, but further high‑quality studies are needed.

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Whole‑exome sequencing for hereditary cancer screening: Whole‑exome sequencing (Exome+) can identify HBOC and Lynch syndrome gene carriers, including individuals not meeting NCCN criteria, but limitations (CNV detection, population representation) and current evidence preclude broad adoption for routine hereditary cancer screening.

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Individuals With a Personal History of a Primary Solid Tumor

Covered when specific tumor types or family/history features are present

Renal cell carcinoma criteria

Histologic features: Multifocal papillary histology; hereditary leiomyomatosis‑associated RCC or RCC with fumarate hydratase deficiency; Birt‑Hogg‑Dubé syndrome‑related histology; angiomyolipomas plus an additional tuberous sclerosis complex criterion; succinate dehydrogenase‑deficient RCC histology.
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Other specified tumor criteria: Coverage includes individuals with serous tubal intraepithelial carcinoma and other tumor‑specific criteria listed in the policy for MGPT eligibility.

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Individuals With No Personal History of a Primary Solid Tumor

Covered when family history meets specified criteria

Family history requirement: Individual's family history includes two or more first‑ or second‑degree relatives on the same side of the family with renal cell carcinoma.

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Genetic testing with a multigene hereditary cancer panel is covered for individuals without a personal history of a Primary Solid Tumor only when specific family-history or risk-score criteria are met. Examples include two or more first‑ or second‑degree relatives on the same side with renal cell carcinoma, two or more second‑degree relatives with Lynch‑associated cancers, three or more close blood relatives on the same side with primary solid tumors, Ashkenazi ancestry plus a relative with a BRCA‑related cancer, or a close relative who meets polyposis diagnostic criteria but is unwilling/unable to be tested. The policy also notes that a Tyrer‑Cuzick, BRCAPRO, or CanRisk score ≥5% for BRCA1/2 or a PREMM5/MMRpro/MMRpredict score ≥5% for Lynch syndrome in an unaffected individual constitutes a covered indication.

The ACMG and specialty society statements emphasize that genetic testing should be targeted to patients where results will influence care; current ACMG guidance does not support routine multigene panel testing for every patient with breast cancer, particularly panels that include genes lacking evidence to change management. Multigene testing may be offered to appropriate candidates after individualized assessment and counseling, and test selection should consider personal and family history and the potential clinical actionability of findings.

Variants of uncertain significance (VUS) are not clinically actionable and should not be used to change medical management. Professional society guidance (ASCO/SSO and ACMG) explicitly states that VUS findings should not drive clinical interventions, and genetic counseling is required to explain the limitations and implications of VUS results.

Panels that include genes with limited or no evidence linking them to cancer risk may yield results that are not clinically actionable and can create management uncertainty. Larger panels often include low‑ or moderate‑risk genes for which evidence about appropriate management is limited; selecting such panels may lead to findings without clear surveillance or intervention pathways.

Concerns about broad panel use include an increased likelihood of detecting VUSs as panel size grows and the risk that clinicians, in the absence of genetic expertise, may act inappropriately on uncertain findings. The policy cautions that identification of variants of unclear clinical significance can prompt unnecessary follow‑up testing or procedures and underscores the need for genetic counseling and specialist involvement when ordering larger panels.

Current evidence is insufficient to support routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels. While RNA testing can clarify some splicing variants and has been shown to modestly increase diagnostic yield in select studies, the available studies are limited in size and quality; the policy therefore recommends considering RNA testing as a follow‑up to inconclusive DNA results rather than as a routine concurrent test.

Whole‑exome and whole‑genome sequencing for the specific purpose of identifying hereditary cancer syndromes or estimating hereditary cancer risk is considered unproven and not medically necessary for routine clinical use. Although exome‑scale testing can identify carriers not meeting guideline criteria in research cohorts, limitations in detection of certain variant types, population representation, and clinical utility preclude broad clinical adoption for hereditary cancer screening.

RNA panel testing, polygenic risk scoring (PRS), and whole‑exome/genome sequencing are categorized as experimental or not medically necessary for routine hereditary cancer indications. The policy specifies that RNA panels and PRS are unproven for routine use and that WES/WGS for identifying hereditary cancer syndromes or risk is not medically necessary outside of defined clinical indications or research contexts.

Multigene panels that include genes with limited or no evidence of association with disease and that lack demonstrated impact on clinical management are of uncertain utility. The policy highlights limited guideline support for comprehensive multisyndrome panels and recommends selecting panel composition based on the suspected syndrome(s) and available evidence to ensure results will inform care.

Use of comprehensive multisyndrome panels to guide clinical management has minimal support in the published literature and lacks clear guideline backing in some contexts. Evidence reviews identified few studies that compared broad multisyndrome panels with targeted testing or reported clinical outcomes, limiting confidence that comprehensive panels improve patient management over focused, syndrome‑directed testing.

Use of polygenic risk scores (PRS) for assessing hereditary cancer risk is currently insufficiently supported by the evidence to guide routine clinical decision‑making. PRS may improve discrimination when combined with clinical factors, but limitations including population generalizability and modest predictive performance when used alone restrict their clinical utility at present.

The ACMG advises caution with clinical implementation of PRS: routine use is not supported unless providers and patients thoroughly understand PRS limitations and there is evidence that results will change management. The policy therefore does not endorse standalone clinical use of PRS to direct interventions without supporting evidence and counseling.

Whole‑exome and whole‑genome sequencing to identify hereditary cancer syndromes or to estimate hereditary cancer risk are not considered medically necessary for routine clinical use. While exome‑scale screening can detect HBOC and Lynch gene carriers in selected studies, the policy notes methodological and clinical limitations and classifies WES/WGS for this purpose as unproven.

Covered Indications and Specific Testing Scenarios

See detailed personal-history and family-history criteria for BRCA1/2 or multigene hereditary cancer panel testing.

See detailed personal‑history and family‑history criteria for BRCA1/2 or multigene hereditary cancer panel testing.

Refer to detailed criteria: Detailed personal‑ and family‑history criteria for BRCA1/2 and MGPT are enumerated in the policy sections covering individuals with and without a personal history of a Primary Solid Tumor; these include age cutoffs, tumor features, tumor testing results, and family history permutations.

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Personal or family history consistent with hereditary cancer susceptibility where results will influence management.

Personal or family history consistent with hereditary cancer susceptibility (early‑onset disease, multiple affected relatives, syndromic features) where results will influence management — testing indicated when it can be interpreted and will inform diagnosis, surveillance, prevention, or treatment.

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Applicable Procedure and Billing Codes

Applicable molecular pathology and panel codes (selection)mixed

0138U	BRCA1 and BRCA2 mRNA sequence analysis (list separately)
81162	BRCA1/BRCA2 full sequence analysis and full duplication/deletion analysis
81163	BRCA1/BRCA2 full sequence analysis
81164	BRCA1/BRCA2 full duplication/deletion analysis
0101U	Hereditary colon cancer disorders panel, 15 genes (sequencing and deletion/duplication), EPCAM and GREM1 deletion/duplication only
0102U	Hereditary breast cancer-related disorders panel, 17 genes (sequencing and deletion/duplication)

Additional applicable molecular pathology, panel, exome/genome codesmixed

0103U	Hereditary ovarian cancer panel, 24 genes
0129U	Hereditary breast cancer-related disorders panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, TP53)
0130U	Targeted mRNA sequence analysis panel for hereditary colon cancer disorders (list separately)
0133U	Hereditary prostate cancer-related targeted mRNA panel (11 genes)
0134U	Hereditary pan-cancer targeted mRNA sequence analysis panel (18 genes)
0162U	Hereditary colon cancer (Lynch) targeted mRNA panel (MLH1, MSH2, MSH6, PMS2)
0238U	MLH1, MSH2, MSH6, PMS2, EPCAM comprehensive genomic DNA analysis
0474U	Hereditary pan-cancer 88-gene NGS panel
0475U	Hereditary prostate cancer 23-gene NGS panel
0495U	Oncology (prostate) circulating plasma proteins and germline polygenic risk score (60 variants)

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Whole exome/genome and related proprietary codesmixed

0212U	Rare diseases, whole genome and mitochondrial DNA sequence analysis, identification and categorization of genetic variants
0213U	Whole genome and mitochondrial DNA sequence analysis, identification and categorization, each comparator genome
0214U	Whole exome and mitochondrial DNA sequence analysis, proband
0215U	Whole exome and mitochondrial DNA sequence analysis, each comparator exome
0265U	Whole genome and mitochondrial DNA sequence analysis, blood/FFPE/frozen tissue, identification of SNVs and CNVs
0266U	Tissue-specific gene expression by whole-transcriptome and NGS, reported as splicing or expression change
81415	Exome; sequence analysis
81416	Exome; sequence analysis, each comparator exome
81417	Exome; re-evaluation of previously obtained exome sequence

Genome sequencing and unlisted molecular pathologymixed

81425	Genome; sequence analysis
81426	Genome; sequence analysis, each comparator genome
81427	Genome; re-evaluation of previously obtained genome sequence
81479	Unlisted molecular pathology procedure

Multigene Panel - Removed CodesCPTNot Covered

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

Whole Exome and Whole Genome Sequencing - Added CodesCPT

0212U	Whole Exome/Genome sequencing - added
0213U	Whole Exome/Genome sequencing - added
0214U	Whole Exome/Genome sequencing - added
0215U	Whole Exome/Genome sequencing - added
0265U	Whole Exome/Genome sequencing - added
0266U	Whole Exome/Genome sequencing - added
81415	Whole Exome/Genome sequencing - added
81416	Whole Exome/Genome sequencing - added
81417	Whole Exome/Genome sequencing - added
81425	Whole Exome/Genome sequencing - added

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Risk model thresholds — BRCA and Lynch

BRCA1/2 risk threshold (personal history)Tyrer-Cuzick, BRCAPRO, or CanRisk score ≥ 2.5% for a BRCA1/2 pathogenic variant

BRCA1/2 risk threshold (unaffected individuals)Tyrer-Cuzick, BRCAPRO, or CanRisk score ≥ 5% for a BRCA1/2 pathogenic variant

Lynch syndrome predictive models (personal history)PREMM5, MMRpro, or MMRpredict score ≥ 2.5% for having a Lynch syndrome gene mutation

Lynch syndrome predictive models (unaffected individuals)PREMM5, MMRpro, or MMRpredict score ≥ 5% for having a Lynch syndrome gene mutation

PREMM5/MMR predictive model score

Ordering, Documentation, and Authorization Guidance

Documentation Required

Codes referenced; documentation may be required

The following procedure and diagnosis codes are provided for reference and may be required with prior authorization or medical review. Listing does not guarantee coverage or payment; additional codes may apply. Medical records documentation may be requested to determine whether the member meets clinical criteria.

Key CPT/HCPCS and proprietary codes for WES/WGS and exome procedures: 0212U, 0213U, 0214U, 0215U, 0265U, 0266U, 81415, 81416, 81417, 81425, 81426, 81427, 81479
Unlisted molecular pathology procedure: 81479
Proprietary/other molecular codes listed in policy used for whole exome/genome sequencing and related services

Prior Authorization

Panel selection and counseling

When ordering germline multigene panels (MGPT), document the clinical rationale for the specific panel chosen and include evidence of genetic counseling or a plan for pre- and post-test counseling. Select panels that include the genes most relevant to the patient's personal and family history; justify inclusion of broader panels when genes of uncertain utility are included.

Member Eligibility and Test Authorization Requirements

For coverage of unaffected (no personal history) individuals, detailed family history is required and must meet specified patterns such as two or more first‑ or second‑degree relatives on the same side with renal cell carcinoma, multiple relatives with Lynch‑associated cancers, or other enumerated family configurations. The policy emphasizes documentation of pedigree and family history to support medical necessity when testing unaffected individuals.

Coverage for unaffected individuals also includes situations where risk‑model thresholds are met (for example, a Tyrer‑Cuzick, BRCAPRO, or CanRisk score ≥5% for BRCA1/2 or a PREMM5/MMRpro/MMRpredict score ≥5% for Lynch syndrome) or when a family member meets diagnostic criteria for polyposis but is unwilling or unable to undergo testing. These criteria require appropriate documentation of family history and risk scores.

The policy lists several family‑history permutations that qualify an unaffected person for multigene panel testing, including three or more close blood relatives on the same side with primary solid tumors (excluding basal/squamous skin cancers) and Ashkenazi Jewish ancestry with at least one relative with a BRCA‑related cancer. Documentation of the pedigree and relatives' diagnoses and ages is necessary to establish eligibility.

When ordering testing for unaffected individuals, the policy expects detailed clinical documentation to be submitted: a pedigree using standardized nomenclature, a comprehensive family history covering first‑ to third‑degree relatives with ages at diagnosis, primary tumor sites, bilateral disease, and current age or age at death. This documentation supports assessment of whether family patterns meet covered indications.

Single‑gene testing and testing for a known familial pathogenic/likely pathogenic variant are considered proven and medically necessary when applicable. Tumor testing results that suggest germline implications may also guide subsequent germline testing decisions; when feasible, testing an affected relative first is preferred as it is more informative than testing an unaffected individual.

Services Considered Not Medically Necessary / Experimental

The policy explicitly lists tests considered not covered: RNA panel testing for hereditary cancers, genetic testing intended for polygenic risk scoring for hereditary cancers, and whole‑exome and whole‑genome sequencing when performed to identify hereditary cancer syndromes or estimate hereditary cancer risk are categorized as unproven and not medically necessary for routine clinical use.

Routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels is not covered due to insufficient evidence. Although select studies show RNA testing can clarify some variants and modestly increase diagnostic yield, limitations in study design and lack of consensus on interpretation standards prevent routine coverage.

Standalone use of polygenic risk scores to guide clinical management is not covered. The ACMG cautions that PRS lack sufficient evidence for routine clinical implementation, have limited generalizability across ancestries, and should not alone determine medical interventions without a clear evidence base and counseling.

Routine testing of all patients with breast cancer using multigene panels that include genes lacking evidence to influence management is not supported. Professional society guidance recommends individualized assessment and targeted test selection; indiscriminate panel testing is discouraged.

The policy explicitly discourages using VUS findings to change clinical management. Panels or test selections that increase the likelihood of VUS detection without clear management pathways are not supported and may be considered not covered when used to justify irreversible interventions.

Comprehensive multisyndrome panels used broadly without demonstrated impact on clinical management or lacking guideline support may be considered not covered. Evidence reviews found minimal support for routine use of broad multisyndrome panels to alter clinical outcomes compared with targeted, syndrome‑directed testing.

Definitions and Key Terms

BRCA‑Related Cancers (definition)

Defined BRCA‑related cancersBreast cancer; ovarian cancer (including fallopian tube and primary peritoneal cancer); pancreatic adenocarcinoma; prostate cancer

ContextTerm used to identify cancers associated with BRCA1/2 pathogenic variants per NCCN definitions

Policy useListed as qualifying personal or family history cancers when assessing HBOC risk

Multigene Panel

Multigene panel definitionGenetic tests using next-generation sequencing to analyze multiple genes simultaneously; for this policy, defined as panels consisting of five or more genes

SynonymsAlso called multigene test or multiple-gene panel test

Background and Evidence Summary

Hereditary cancer genetic testing identifies germline variants that increase risk for specific cancers (for example, BRCA‑related cancers and Lynch syndrome). Pretest genetic counseling is strongly recommended to explain the advantages, limitations, and potential downstream implications of testing, and testing approaches commonly include single‑gene testing, targeted founder variant analysis, or multigene panels (defined in this policy as five or more genes).

5-10%Estimated cancers that are hereditary

14.2%CRC patients with ≥1 P/LP variant (Coughlin et al.)

15.5%Pathogenic variants in universal >80‑gene CRC MGPT (Uson et al.)

9%Pathogenic mutations detected after prior BRCA1/2‑negative testing (Crawford et al.)

Exome‑scale sequencing in research or selected study populations has identified carriers of HBOC and Lynch syndrome genes who did not meet guideline‑based testing criteria; these findings suggest potential utility of broader sequencing approaches in selected contexts but do not, by themselves, establish routine clinical coverage.

Policy Revision History

2026-05-01material_revisionLatest

Revised coverage criteria for Multigene hereditary cancer panel for individuals with a personal history of a Primary Solid Tumor: added serous tubal intraepithelial carcinoma and expanded renal cell carcinoma criteria (age ≤46 at diagnosis, bilateral/multifocal disease, family history of RCC, personal/family history of mesothelioma or uveal melanoma) and specified RCC histologic features; replaced PENN11 with CanRisk in BRCA1/2 risk model options; revised ovarian cancer examples.

2026-05-01added_statement

Added language that whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes or risk is unproven and not medically necessary.

Policy Summary

PayerUnitedHealthcare

PolicyGenetic Testing for Hereditary Cancer (Nebraska)

Policy CodePolicy CS049NE.E

Change TypeRevisions to coverage criteriaadded WES/WGS languagecode updates

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionWhen ordering germline multigene panel testing, include rationale for panel choice and document pretest genetic counseling or a plan for counseling.

SourceLink

On This Page

NCCN ovarian criteria

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

NCCN pancreatic criteria

Prostate cancer-specific indications: Personal history of metastatic or high/very‑high risk prostate cancer; family history including relatives with early breast cancer, male breast cancer, ovarian, pancreatic, or metastatic/high‑risk prostate cancer; ≥3 close relatives with breast and/or prostate cancer on same side; Ashkenazi Jewish ancestry; or unaffected/affected patients with a first‑degree relative meeting criteria.

NCCN prostate criteria

Pancreatic adenocarcinoma: Germline testing using comprehensive panels is recommended for any patient with confirmed pancreatic cancer or clinical suspicion; genetic counseling is recommended for mutation‑positive patients.

NCCN Pancreatic v2.2025

Neuroendocrine and adrenal tumors: Genetic risk evaluation/testing recommended for patients meeting specified criteria (pheochromocytoma/paraganglioma, adrenocortical carcinoma, MEN features, tumor PVs with germline implications, or close relative with P/LP variant); multigene testing may be efficient due to overlapping syndromes.

NCCN NETs v2.2024

Kidney cancer: Genetic risk evaluation/testing should be considered for RCC patients with early age at diagnosis (<=46), bilateral/multifocal tumors, family history, specific histologic features, or close relative with known P/LP variant.

NCCN Kidney v1.2026

Clinically indicated testing per NCCN and specialty society criteria for personal or family histories of multiple cancers

NCCN and specialty society criteria: Clinically indicated testing per NCCN and specialty society criteria for personal or family histories of breast, ovarian, pancreatic, prostate, colorectal, endometrial, and gastric cancers as detailed in the criteria sets; see syndrome‑specific blocks for exact permutations.

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Evaluation for Lynch syndrome, adenomatous polyposis, hamartomatous polyposis syndromes, PPGL, pancreatic cancer, renal cell carcinoma, and other hereditary cancer syndromes when clinical criteria or family history met as specified by guidelines.

Syndrome evaluations: Evaluation for Lynch syndrome, adenomatous polyposis, hamartomatous polyposis syndromes, pheochromocytoma/paraganglioma (PPGL), pancreatic cancer, renal cell carcinoma, and other hereditary cancer syndromes when clinical criteria or family history meet guideline thresholds.

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Patients with cancer meeting guideline-specified criteria including specific tumor types and clinical features where multigene testing is recommended or strongly recommended.

Patients with cancer meeting guideline-specified criteria: Patients with cancer who meet guideline‑specified criteria (ASCO, NCCN) — including specific tumor types, age, family history, and histologic features — should be offered germline multigene testing that includes at minimum the more strongly recommended genes for the cancer type.

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Identification of HBOC and Lynch syndrome gene carriers via exome sequencing in research/selected study populations (evidence noted but not universal coverage implication).

Exome detection of HBOC/LS carriers: Whole‑exome/Exome+ sequencing in research/selected study populations has identified carriers of HBOC and Lynch syndrome genes, including individuals not meeting NCCN criteria; evidence noted but not a basis for universal coverage.

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Multigene hereditary cancer panel for individuals with a personal history of a Primary Solid Tumor meeting specified tumor-type, age, family history, or histology criteria.

MGPT for individuals with Primary Solid Tumor: Multigene hereditary cancer panel is covered for individuals with a personal history of a Primary Solid Tumor when specified tumor‑type, age, family history, or histology criteria are met (including serous tubal intraepithelial carcinoma and detailed renal cell carcinoma criteria).

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Testing for individuals with no personal history of a Primary Solid Tumor when family history includes two or more first- or second-degree relatives on same side with renal cell carcinoma.

Unaffected individuals with RCC family history: Testing is covered for individuals with no personal history of a Primary Solid Tumor when family history includes two or more first‑ or second‑degree relatives on the same side with renal cell carcinoma.

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Primary PREMM5/MMR thresholdPredictive model score ≥ 5% predicted probability of a germline MMR P/LP variant (eg, PREMM5, MMRpro, MMRpredict)

Lower PREMM5/MMR threshold for certain contextsFor patients with no personal history of CRC/EC, a PREMM5 score ≥ 2.5% may be used (with clinical judgment) to select individuals for MMR testing

Role in Lynch evaluationModel scores should be documented alongside personal/family history and tumor dMMR/MSI results when available

Adenoma count threshold

Adenoma count threshold (primary)Testing is recommended when a patient has 20 or more cumulative adenomas

Intermediate adenoma countsConsider testing for patients with 10–19 cumulative adenomas or related tumors per additional criteria

Family or tumor triggersAlso recommend testing when there is a known familial PV in an adenomatous polyposis gene or compatible clinical features (eg, congenital hypertrophy of the retinal pigment epithelium)

BRCA1/2 risk score threshold

BRCA1/2 model thresholdTyrer-Cuzick, BRCAPRO, or CanRisk score of ≥ 2.5% for a BRCA1/2 pathogenic variant

Model examplesAcceptable risk models include Tyrer-Cuzick, BRCAPRO, and CanRisk (PENN11 replaced by CanRisk in the 05/01/2026 revision)

Use with clinical featuresRisk-model results are considered alongside personal and tumor features when determining testing appropriateness

Include minimum gene sets recommended by disease-specific guidelines when applicable (e.g., CRC/EC panels per NCCN)
Provide rationale if ordering broader panels (e.g., to capture multiple phenotypes or when prior limited testing was negative)
Document plan for genetic counseling by a trained genetics professional or provider with expertise in cancer genetics

Documentation Required

Specialist involvement and counseling

When multigene panels include genes of uncertain clinical utility or when results will influence complex management decisions, involve providers with expertise in cancer risk assessment (e.g., certified genetic counselors, medical geneticists, or clinicians experienced in cancer genetics). These specialists should participate in pre-test counseling, consent, result interpretation, and family cascade testing recommendations.

Referral recommended when testing includes low/moderate-penetrance or uncertain-utility genes
Specialist involvement expected for complex histories, interpretation of VUS, or when multi-gene results may change treatment/surgical decisions

Billing Rule

WES/WGS Codes Added

Newly added CPT and proprietary codes for whole-exome and whole-genome sequencing are included in the applicable codes and may be subject to review or prior authorization. Plan reviewers may request supporting clinical documentation to determine medical necessity for WES/WGS.

Added codes: 0212U, 0213U, 0214U, 0215U, 0265U, 0266U, 81415, 81416, 81417, 81425, 81426, 81427
Note: Whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes is considered unproven/not medically necessary per policy unless specific criteria are met

Documentation Required

Documentation and clinical evaluation

Medical necessity determinations rely on adequate clinical evaluation and documentation. The patient's medical record must include a detailed personal and family history, physical exam findings, relevant prior genetic test results, and any tumor testing data that support the indication for germline testing. Lack of supporting documentation may result in denial.

Provide first–third degree family history with ages at diagnosis and current age or age at death
Include prior genetic testing reports and prior probability model results (e.g., BRCAPRO, PREMM5) when available
Submit tumor dMMR or tumor genomic findings if relevant to germline testing

Denial Risk

Risks of large panels

Large multigene panels increase the likelihood of detecting variants of uncertain significance (VUS) and may include genes with limited or unknown clinical management implications. Select panels thoughtfully and document how potential uncertain results will be managed.

Discuss the increased probability of VUS with larger panels and document counseling about potential downstream testing and surveillance implications
If genes with limited management data are included, document why their inclusion is clinically justified

Denial Risk

Risk of inappropriate action on uncertain results

Uncertain or inconclusive results (e.g., VUS) are not clinically actionable. Ordering clinicians must be prepared to manage ambiguous findings and avoid inappropriate medical or surgical actions based solely on uncertain results. Document counseling provided regarding limitations of testing and follow-up plans.

Do not base irreversible interventions on VUS alone; record discussions and rationale for any management decisions influenced by genetic results
Document plans for cascade testing of relatives only when P/LP variants are identified

Documentation Required

Pedigree and clinical documentation

A contemporaneous pedigree drawing/diagram using standardized nomenclature is expected to be included with testing requests. The pedigree should be part of the submitted medical records and accompany prior authorization or test-order documentation.

Include a pedigree covering first–third degree relatives with ages at diagnosis and current age or age at death
Use standardized symbols and notation and submit as part of the authorization request

Documentation Required

Required clinical documentation

Required clinical documentation with test orders should include a detailed family history (first–third degree), clinical presentation, prior relevant genetic and tumor testing, and the specific clinical question the test is intended to address. For Lynch syndrome evaluation, include tumor dMMR/MSI results and predictive model scores when available.

Family history: cancer types, ages at diagnosis, bilateral disease, and relation to proband
Prior testing: prior single-gene or limited testing reports and results
Tumor data: dMMR/MSI status, tumor sequencing findings relevant to germline testing

Documentation Required

Genetic counseling by a trained genetics professional expected

Genetic counseling by a trained genetics professional (or an appropriately experienced provider) is expected for pre-test education, informed consent, results disclosure, and discussion of medical management and familial implications. Documentation of counseling or a documented plan to provide counseling should accompany testing requests.

Document that informed consent was obtained and that risks, benefits, limitations, and potential outcomes were discussed
If counseling will be provided after testing, include a documented plan and timeline

Documentation Required

Required clinical documentation for LS evaluation

For Lynch syndrome (LS) evaluations, document elements that meet LS testing criteria: personal and family history of LS-related cancers, age at diagnosis, number and degree of affected relatives, PREMM5 or other predictive model scores, and tumor dMMR/MSI results if available.

Report PREMM5 score and indicate if ≥ 2.5% (for selection guidance) where applicable
Include tumor dMMR/MSI testing results and indicate how they support germline testing

Documentation Required

Family history and counseling documentation

A comprehensive family history should be taken and recorded for all patients being considered for genetic testing. Document psychosocial assessment, informed consent discussion, education about genetics and testing limitations, and plans for result disclosure and family communication.

Record psychosocial assessment and counseling discussions
Document education provided about the likelihood of identifying P/LP variants and the implications for relatives

Prior Authorization

Suggested documentation when ordering advanced genetic tests

When ordering advanced tests (e.g., concurrent RNA testing, WES/WGS), include prior DNA test results, clear rationale for concurrent testing, and clinical and family history that justify use of advanced modalities. Be prepared to submit prior variant data and explain how results may change management.

Provide prior DNA testing reports and variant classifications
State clinical intent for RNA or WES/WGS (e.g., clarify splicing variants after inconclusive DNA testing)
If requesting concurrent RNA testing, document why RNA will be expected to alter classification or management

Note

Documentation updates

Policy updates include additions to definitions, updated documentation expectations, and code list revisions. Verify that submitted documentation aligns with the most recent policy definitions and code lists when requesting authorization or submitting claims.

Updated definitions: Personal and Family History Documentation, PREMM5, etc.
Codes removed and added per latest revision — confirm current applicable codes before submission

Documentation Required

Stepwise vs panel testing; when possible test an affected relative first

Order strategy (stepwise single-gene testing versus MGPT) should be justified in the record. Stepwise targeted testing is preferred when a single syndrome is most likely; MGPT may be more efficient when multiple syndromes are possible or prior limited testing was negative.

Document rationale for choosing MGPT over stepwise testing (e.g., multiple phenotypes, prior negative limited testing)
When feasible, test an affected relative first to maximize diagnostic yield and interpretability

Prior Authorization

Panel size and sequencing (panel size sequencing)

When rapid therapeutic decisions are required, consider initial use of smaller, targeted panels; larger panels can follow later. Document the clinical need for faster turnaround when ordering limited panels for treatment decision-making.

Use smaller panels when results are urgently needed for systemic therapy or surgical planning
If ordering a large panel for non-urgent indications, document why broader testing is preferred

Documentation Required

Step approach: consider RNA after inconclusive DNA

Consider RNA testing after inconclusive DNA results to clarify splicing or expression effects; concurrent RNA testing with initial DNA panels is considered investigational/insufficient evidence per policy unless justified. Document prior DNA findings that prompt RNA follow-up.

Order RNA testing primarily as a follow-up to inconclusive DNA results and include prior DNA reports
If concurrent RNA/DNA testing is requested, include strong rationale and expected impact on diagnostic yield or management

Documentation that prior targeted testing was negative but clinical suspicion remains (for example, prior BRCA1/2 testing followed by continued high clinical risk) supports consideration of expanded multigene panel testing. The policy notes that affected‑first testing and prior test results should be included in the record to justify further testing.

PRS for hereditary cancer risk assessment is not supported as standard coverage given current evidence limitations. The policy notes concerns about generalizability, modest predictive performance when used alone, and the need for evidence that PRS results change management and outcomes.

Routine concurrent RNA panel testing with BRCA1/2 or multigene hereditary cancer panels is listed as not covered due to insufficient high‑quality evidence supporting routine concurrent use; RNA testing may be considered as a follow‑up to clarify inconclusive DNA findings in selected cases.

The policy reiterates that standalone clinical use of PRS to guide management is not covered absent a thorough understanding of limitations and supporting evidence, consistent with ACMG recommendations.

Whole‑exome and whole‑genome sequencing to identify hereditary cancer syndromes or estimate hereditary cancer risk are designated as not covered for routine use. Although exome‑scale approaches can detect carriers not meeting guideline criteria in research cohorts, the policy classifies WES/WGS for this purpose as unproven and not medically necessary outside defined clinical or research contexts.

Typical contentPanels often include sequencing plus large deletion/duplication analysis

Limited Family History

Limited family history — definitionFewer than two known first‑degree or second‑degree female relatives surviving beyond age 45 on either or both sides of the family

Clinical implicationMay affect interpretation of risk and selection of testing strategies (eg, consider broader testing when family history is limited)

Example scenariosApplies to individuals with adoption or sparse family information

Hereditary cancer susceptibility testing

PurposeGenetic testing performed to identify inherited variants that increase an individual's risk of developing cancer

Informed by historyTypically informed by personal and family history and used to guide surveillance, prevention, and treatment

Testing typesIncludes single-gene, multigene panels, and selected advanced genomic assays depending on indication

Multigene hereditary cancer panel

MGPT definitionNext‑generation sequencing–based test that analyzes multiple genes associated with increased cancer risk, often including sequencing and deletion/duplication analysis

Panel sizePanels in practice range from ≥5 genes to >80 genes depending on vendor and indication

Clinical considerationsPanel composition should be guided by phenotype and management implications to avoid identifying genes of uncertain utility

MGPT (Multigene Panel Testing)

MGPT (abbreviation)NGS‑based testing that evaluates multiple genes simultaneously for pathogenic/likely pathogenic variants associated with hereditary cancer

IncludesUsually includes full gene sequencing and deletion/duplication analysis; may include large panels with low/moderate penetrance genes

Counseling implicationPre- and post-test genetic counseling recommended when MGPT is performed

Variant of Uncertain Significance (VUS)

Variant of uncertain significance (VUS)Genetic finding without sufficient evidence to determine pathogenicity; not clinically actionable and should not change management

Impact on practiceVUS results should not be used to direct medical or surgical management; counseling should explain VUS implications

Panel size effectLarger panels increase likelihood of detecting VUSs and may complicate interpretation

Lynch syndrome

Lynch syndrome definitionCondition defined by germline heterozygous pathogenic/likely pathogenic variants in MMR genes MLH1, MSH2, MSH6, PMS2, or 3' EPCAM deletions

Associated cancersIncludes colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, brain, biliary tract, small intestine, sebaceous skin tumors

Testing triggersFamily history of known LS PV, tumor dMMR/MSI, or predictive model scores guide evaluation

Adenomatous polyposis testing indications

Primary indication — adenomatous polyposisTesting recommended for patients with ≥20 cumulative adenomas

Additional indicationsAlso recommended for known familial PV in an adenomatous polyposis gene or related clinical features (eg, congenital hypertrophy of retinal pigment epithelium)

Consideration rangeConsider testing for patients with 10–19 adenomas or certain associated tumors per guidance

Polygenic risk score (PRS) — summary and limitations

Polygenic risk score (PRS) — definitionComposite score derived from multiple SNPs intended to estimate genetic predisposition to common diseases

Performance and limitationsPRS alone shows modest discriminatory ability (eg, pooled AUC ~0.63 for prostate cancer) and may improve when combined with clinical variables

Clinical stanceEvidence insufficient to support routine clinical implementation for hereditary cancer risk without clear management evidence

Polygenic Risk Score (PRS)

PRS — technical definitionA composite score derived from multiple SNPs intended to estimate genetic predisposition to common diseases; performance varies by ancestry and methodology

Clinical performancePooled AUC for prostate cancer PRS ~0.63 alone and ~0.74 when combined with clinical variables

Implementation cautionACMG does not support routine clinical implementation of PRS without understanding limitations and management evidence

Concurrent RNA panel testing

Concurrent RNA panel testing — definitionRNA sequencing/panel testing performed alongside DNA testing to evaluate splicing and transcript effects

Diagnostic yieldRNA testing may clarify some variants and modestly increase diagnostic yield (eg, a reported 9.1% relative increase in one study), but overall evidence is limited

Policy stanceInsufficient evidence to support routine concurrent RNA panel testing with BRCA1/2 or multigene panels

Whole‑exome sequencing (WES/Exome+)

Whole‑exome sequencing (WES/Exome+) — definitionBroad sequencing of coding regions to identify germline variants in hereditary cancer genes

Potential utilityWES can detect HBOC and Lynch carriers including some who do not meet NCCN criteria in selected studies

LimitationsMay miss CNVs and noncoding variants; population representation and technical limits constrain broad adoption; considered unproven/not medically necessary for routine hereditary cancer identification

Primary Solid Tumor (policy context)

Primary Solid Tumor — notePolicy references Primary Solid Tumor in coverage criteria; updated definition in policy (see definitions)

UsageUsed throughout coverage criteria to distinguish qualifying tumors from non-qualifying skin cancers (eg, basal or squamous cell)

ContextRelevant for personal-history–based testing eligibility (eg, tumor histology triggers)

PREMM5

PREMM5 — definitionPREMM5 is a predictive model estimating cumulative probability of having an MLH1, MSH2, MSH6, PMS2, or EPCAM gene mutation (Lynch syndrome)

Clinical usePREMM5 scores are used alongside family/personal history and tumor dMMR status to select individuals for MMR gene testing

Threshold notesPolicy references PREMM5 thresholds (≥2.5% or ≥5%) for Lynch evaluation depending on context

For individuals with no personal history of a Primary Solid Tumor, added family-history requirement of two or more first- or second-degree relatives on the same side with renal cell carcinoma.

2026-05-01code_removal

Removed CPT codes 0131U, 0132U, and 0135U from the Multigene Panel applicable codes listing.

2026-05-01code_addition

Added CPT codes for Whole Exome and Whole Genome Sequencing: 0212U, 0213U, 0214U, 0215U, 0265U, 0266U, 81415, 81416, 81417, 81425, 81426, and 81427.

The policy references BRCA1/2 risk‑model thresholds and documents a revision effective 05/01/2026 replacing a prior PENN11 reference with acceptance of Tyrer‑Cuzick, BRCAPRO, or CanRisk scoring for assessing a 2.5% or greater probability of a BRCA1/2 pathogenic variant in certain contexts; other thresholds (eg, 5% for unaffected individuals) are referenced elsewhere in the criteria.