sierra health and life hereditary cancer Coverage Update | OpenPayer
Modifiedsierra health and lifePolicy 2026T0009TT
Genetic Testing for Hereditary Cancer
Criteria and coverage guidance for germline genetic testing (single-gene and multigene panels, RNA, exome/genome, and polygenic risk) for hereditary cancer risk assessment for UnitedHealthcare Commercial and Individual Exchange plans.
Policy Summary
Payersierra health and life
PolicyGenetic Testing for Hereditary Cancer
Policy CodePolicy 2026T0009TT
Change TypeCoverage criteria revisedcodes addedWES/WGS designated not medically necessary
Effective DateApr 1, 2026
Next Review DateN/A
Key ActionDocument guideline-based clinical criteria and submit contemporaneous pedigree/family-history documentation when requesting prior authorization for germline multigene panel testing.
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 criteria for serous tubal intraepithelial carcinoma and expanded renal cell carcinoma criteria and histologies.
Replaced references to PENN11 score with CanRisk and replaced PENN11 in both 2.5% and 5% BRCA1/2 threshold statements; replaced BRCAPro spelling variants to BRCAPRO.
Added language that whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes or hereditary cancer syndrome risk is unproven and not medically necessary.
Added multiple CPT codes related to whole exome/genome sequencing and other molecular tests to the Applicable Codes section (including 0212U–0215U, 0265U–0266U, 81415–81417, 81425–81427).
Removed definitions for 'High Penetrance Breast Cancer Susceptibility Genes' and 'Penetrance'.
Updated definitions for BRCA-Related Cancers, Lynch Syndrome-Associated Cancer, Ovarian Cancer, and PREMM5.
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.
several
policy revision items summarized
>=11CPT/PLA codes added for WES/WGS and panels
≤65BRCA testing age threshold
2.5% / 5%BRCA risk score thresholds
unprovenRNA / WES / WGS stance
Coverage Criteria for Hereditary Cancer Testing
inv-01: Individuals with a personal history of a Primary Solid Tumor
Covered when ALL of the following are met for individuals with a personal history of a primary solid tumor:
Personal history requirement: Individual has a personal history of a Primary Solid Tumor (excluding basal or squamous cell skin cancer).
BRCA1/2 indication: BRCA1/2 gene testing is medically necessary for individuals with breast cancer diagnosed at age 65 years or younger (BRCA1/2 testing ≤65).
Specified personal-history features warranting MGPT: Multigene hereditary cancer panel is medically necessary when the individual has at least one of the following tumor- or history-based characteristics: 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 in a person of Ashkenazi Jewish ancestry; breast cancer in an individual assigned male at birth; breast or prostate cancer with at least one first- or second-degree relative with a BRCA-related cancer; ovarian cancer (including fallopian tube, primary peritoneal, sex‑cord tumors with annular tubules, hypercalcemic‑type small cell carcinoma of the ovary) or serous tubal intraepithelial carcinoma; pancreatic cancer; metastatic prostate cancer; Lynch syndrome–associated cancers; neuroendocrine tumors (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma); malignant phyllodes tumors; renal cell carcinoma meeting listed age, laterality, family‑history, associated cancers, or histologic features; or at least two different primary solid tumors.
Family-history augmenting personal history: Individual has a personal history of a Primary Solid Tumor and a family history that includes at least one of: a close blood relative with a Lynch syndrome–associated cancer; a close blood relative diagnosed with a primary solid tumor at age ≤40; or at least two close blood relatives on the same side of the family diagnosed with primary solid tumors (excluding basal/squamous skin cancers).
Tumor-guided germline testing trigger: Germline testing is indicated when tumor testing identifies a pathogenic variant with germline implications (examples listed) or when tumor testing demonstrates MSI‑high/dMMR (loss of one or more MMR proteins: MLH1, MSH2, MSH6, PMS2).
Risk-model thresholds (personal history): Individual has a Tyrer‑Cuzick, BRCAPRO, or CanRisk score ≥2.5% for BRCA1/2 or a PREMM5/MMRpro/MMRpredict score ≥2.5% for Lynch syndrome (context‑specific thresholds noted).
inv-02: Individuals with no personal history of a Primary Solid Tumor
Covered when ALL of the following are met for individuals with no personal history of a primary solid tumor:
First-degree relative criteria: At least one first‑degree relative with either (a) two or more different primary solid tumors (excluding basal/squamous cell skin cancer), (b) a Lynch syndrome–associated cancer, or (c) a neuroendocrine tumor (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma).
First- or second-degree relative specific cancers: At least one first‑ or second‑degree relative with breast cancer diagnosed ≤50 years, triple‑negative breast cancer, breast cancer in a relative assigned male at birth, metastatic prostate cancer, ovarian cancer (including fallopian tube or primary peritoneal), or pancreatic cancer.
Second-degree relative criteria: At least one second‑degree relative with two or more Lynch‑associated cancers or a Lynch‑associated cancer diagnosed ≤50 years.
Family aggregation or special family-history patterns:
inv-03: Not medically necessary / unproven tests
Not covered / unproven tests: Multigene hereditary cancer panels, RNA panel testing, polygenic risk scoring, and whole‑exome/whole‑genome sequencing for the purpose of identifying hereditary cancer syndromes or hereditary cancer risk are considered unproven and not medically necessary for indications not specified in this policy.
inv-04: General medical necessity criteria
Covered when ALL of the following are met
General coverage criteria: Genetic testing is appropriate when: (1) the individual's personal or family history is consistent with hereditary cancer susceptibility; (2) the test can be adequately interpreted by available laboratory and clinical resources; and (3) results can be used to diagnose or influence medical management of the individual or at‑risk family members.
inv-05: Pre-test evaluation
Required evaluation prior to testing
Pre-test evaluation requirements: Obtain and document a detailed family history (first‑, second‑, and third‑degree relatives) including ages at diagnosis, primary tumor sites, bilateral disease, current age or age at death; perform a thorough physical exam by a clinician familiar with hereditary cancer syndromes; and apply risk assessment tools when applicable (examples: BRCAPRO, Tyrer‑Cuzick, CanRisk, BOADICEA, PREMM5/MMRpro).
inv-06: Clinically indicated testing (NCCN)
Covered when ANY of the following NCCN clinical-indication scenarios are met (grouped by general and cancer-specific criteria):
NCCN general indications: Any blood relative with a known P/LP variant in a cancer susceptibility gene; prior limited/negative testing with ongoing suspicion and desire for multigene testing; known tumor P/LP variant with germline implications; testing to inform systemic therapy or surgical decision‑making; meeting testing criteria for Li‑Fraumeni, Cowden/PTEN, or Lynch syndromes.
Breast cancer indications (NCCN): Personal history: breast cancer diagnosed ≤50 years; breast cancer at any age when testing will inform PARP/olaparib therapy; triple‑negative breast cancer; multiple primary breast cancers; lobular histology with diffuse gastric cancer in family; male breast cancer; Ashkenazi Jewish ancestry; relevant close relative meeting listed criteria; or >5% BRCA1/2 probability by models (Tyrer‑Cuzick, BRCAPRO, CanRisk).
Ovarian cancer indications (NCCN): All patients with epithelial ovarian/fallopian tube/peritoneal cancer should undergo germline multigene testing at any age; unaffected individuals with a first‑ or second‑degree relative with epithelial ovarian cancer also qualify; >5% BRCA probability by models may qualify.
inv-07: Lynch Syndrome Testing
Testing for Lynch syndrome and related germline MMR defects is recommended when ANY of the following apply:
Known familial MMR variant: Patient has a family history of a known germline MMR pathogenic/likely pathogenic variant.
Personal early-onset CRC/EC: Patient has a personal history of colorectal or endometrial cancer diagnosed at age <50 years.
Tumor dMMR/MSI: Tumor shows deficient mismatch repair (MSI‑high or abnormal MMR IHC) at any age.
Family-history LS patterns: Family history includes first‑ or second‑degree relative(s) with LS‑related cancers diagnosed <50 years, or two or more relatives with LS‑related cancers.
inv-08: Adenomatous Polyposis Testing
Adenomatous polyposis testing is recommended when ANY of the following are met:
>=20 adenomas: Personal history of 20 or more cumulative adenomas.>=20 adenomas
Known familial polyposis variant: Family history of a known pathogenic variant in an adenomatous polyposis gene.
Syndromic phenotypes: Multifocal/bilateral congenital hypertrophy of the retinal pigment epithelium or cribriform‑morular variant of papillary thyroid cancer.
Consider testing 10-19 adenomas: Personal history of 10–19 cumulative adenomas or features such as desmoid tumor/hepatoblastoma — testing may be considered.10-19 adenomas (consider)
inv-09: Minimum panel gene lists (NCCN)
When germline MGPT is used for CRC or EC evaluation, panels should include at minimum the following genes:
Minimum gene content for CRC MGPT: Include at minimum: APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM, BMPR1A, SMAD4, PTEN, STK11, and TP53 for colorectal cancer evaluation.
Minimum gene content for EC MGPT: Include at minimum: MLH1, MSH2, MSH6, PMS2, EPCAM, PTEN, and BRCA1/2 for endometrial cancer evaluation.
inv-10: Evidence summary and rationale for MGPT use
Evidence and testing approach considerations (summarized from studies):
CRC evidence: MGPT in colorectal cancer cohorts identifies clinically actionable pathogenic/likely pathogenic variants in a meaningful proportion (e.g., ~14.2% P/LP rate in a large cohort) with clinically actionable findings across ages and ancestries; VUS rates are substantial (e.g., ~38.2%).
Pancreatic and other solid tumor evidence: Universal MGPT in pancreatic and other solid tumor cohorts detects pathogenic germline variants in ~13–15% of unselected participants and identifies clinically actionable findings missed by guideline‑directed testing in some studies.
PPGL and other tumor-specific evidence: Targeted MGPT for PPGLs and selected tumor types shows high diagnostic yields (e.g., ~27.5% in PPGL cohorts); inclusion of relevant rare genes increases diagnostic yield in these settings.
inv-11: Panel size and interpretation considerations
Guideline caution regarding panel size and interpretation:
Panel size and interpretation considerations: Larger multigene panels increase rates of variants of uncertain significance and may include genes with limited evidence to guide medical management; genetic specialist involvement and pre/post‑test counseling are advised and panel selection should be tailored to clinical context.
inv-12: Covered: Germline multigene panel testing
Covered when ALL of the following are met according to cited guideline recommendations
Guideline-based indication
Personal/family history triggers: Comprehensive family history recorded; close blood relative with known P/LP variant; multiple relatives with same cancer; early‑age diagnosis per tumor‑specific criteria.
Tumor-related triggers: Tumor testing reveals a pathogenic variant in a gene with germline implications or tumor histology suggests a hereditary syndrome—offer germline testing regardless of other criteria.
Tumor types listed by guideline: Specific cancers (breast, colorectal, endometrial, ovarian, pancreatic, prostate, renal, neuroendocrine tumors, PPGL, etc.) with recommended gene lists warrant germline multigene panel testing.
inv-13: Not covered/Investigational: Polygenic risk scores for hereditary cancer risk
Coverage stance on Polygenic Risk Scores (PRS)
PRS coverage stance: Polygenic risk score–based testing or reporting is considered investigational/informational due to insufficient evidence of clinical utility for hereditary cancer risk assessment and is not covered for routine clinical use.
inv-14: Coverage-relevant evidence summaries
Summary coverage-relevant findings and logical implications from the evidence
PRS clinical utility and limitations: PRS alone shows modest discriminatory performance (example: pooled AUC ~0.63 for prostate cancer) and improves when combined with clinical variables; PRS performance depends on derivation population and should not be used in isolation to exclude monogenic risk. Clinical management changes should be evidence‑based and accompanied by documented counseling about limitations.
Concurrent RNA testing evidence: Concurrent RNA panel testing can increase diagnostic yield in some studies (example: ~9.1% relative increase reported) and may reclassify some variants, but the overall evidence quality is insufficient to support routine broad adoption; further high‑quality studies assessing clinical impact are needed.
WES/Exome+ considerations: WES/Exome+ can identify carriers of HBOC and Lynch syndrome genes not captured by guideline‑directed testing (e.g., Exome+ found ~1.24% carrier rate for HBOC/LS in a large cohort with many newly identified carriers), but method limitations (reduced CNV detection, population representation biases) and uncertain downstream management support that population screening approaches require more evidence before routine adoption.
inv-15: Individuals With a Personal History of a Primary Solid Tumor (selected excerpts)
Covered when ALL of the following are met (selected excerpts shown in this document portion):
Personal history - selected new RCC and related criteria: Individual has serous tubal intraepithelial carcinoma OR has renal cell carcinoma meeting any of: diagnosed ≤46 years; bilateral or multifocal tumors; one or more first‑ or second‑degree relatives with renal cell carcinoma; personal or family history of mesothelioma or uveal melanoma; OR renal cell carcinoma with histological features such as multifocal papillary histology, HLRCC‑associated histology or fumarate hydratase deficiency features, Birt‑Hogg‑Dube‑related histology, angiomyolipomas plus one additional tuberous sclerosis complex criterion, or succinate dehydrogenase–deficient RCC histology.
inv-16: Individuals With No Personal History of a Primary Solid Tumor (selected excerpts)
Covered when ALL of the following are met (selected excerpts shown in this document portion):
Family history criteria for RCC and BRCA risk scores: Family history includes either two or more first‑ or second‑degree relatives on the same side with renal cell carcinoma OR a first‑degree relative meeting criteria for genetic evaluation for renal cell carcinoma but unwilling/unable to have genetic testing; and the individual has a Tyrer‑Cuzick, BRCAPRO, or CanRisk BRCA1/2 pathogenic‑variant probability score ≥5%.
The policy considers several test types as unproven and not medically necessary for hereditary cancer indications when used outside the specified criteria. Specifically, multigene hereditary cancer panels (when used for indications not listed), RNA panel testing, polygenic risk scoring (PRS), whole-exome sequencing (WES) and whole-genome sequencing (WGS) are described as unproven and not medically necessary for all other indications. These modalities may be appropriate only when they meet the policy's listed clinical indications or are used in research contexts; otherwise they are not covered.
Broad multigene panels that include many low- to moderate-risk genes can identify variants of uncertain significance or gene findings lacking evidence to guide management. Guidelines note panels can be efficient when multiple syndromes are suspected, but larger panels increase VUS rates and may include genes without well-established clinical actionability; this limits clinical utility and supports restricting broad panel use to situations where guideline-based indications and a clear plan for management and counseling exist.
Professional guidance emphasizes targeted screening of women for BRCA-related risk by assessing personal and family history or ancestry. The USPSTF recommends primary care screening with validated family-history tools and genetic counseling for those with positive screens, but does not support routine genetic testing or counseling in individuals without a personal or family history or ancestry associated with increased BRCA1/2 risk.
The USPSTF specifically recommends against routine BRCA counseling or testing (grade D) for women whose personal or family history or ancestry is not associated with an increased probability of a harmful BRCA1/2 mutation. Women with positive screening results should receive genetic counseling and, if indicated after counseling, testing.
The policy discourages ordering multigene panels solely to generate reports of variants of uncertain significance (VUS). Large panels substantially increase the likelihood of VUS findings and may lead to uncertain or unnecessary follow-up; panels should be used when results are reasonably expected to inform clinical management and when counseling resources are available.
Professional societies note important limitations of polygenic risk scores (PRS). The ACMG warns that an isolated PRS should not replace established genetic testing when a monogenic etiology is suspected and that PRS performance is population-dependent; current evidence is insufficient to support routine clinical implementation of PRS for hereditary cancer risk assessment.
Whole-exome and whole-genome sequencing are recognized to identify some carriers of HBOC and Lynch genes in research or cohort contexts, but the policy states these approaches are unproven and not medically necessary for the purpose of identifying hereditary cancer syndromes or hereditary cancer syndrome risk for routine clinical use. Method limitations and need for further evidence are noted.
Overall, the policy summarizes that RNA panel testing, polygenic risk scoring, and whole-exome/whole-genome sequencing for hereditary cancer indications are considered investigational or unproven and are not medically necessary for indications outside those explicitly defined in the policy.
The policy cautions against routine, unselected population-wide multigene testing. Population-based screening using large panels that include many genes with limited clinical validity may identify low-frequency variants with unclear management implications; evidence for net benefit of such unselected testing is limited and routine population-wide MGPT is not supported.
Genetic testing is discouraged for individuals who do not have a personal or family history or ancestry associated with increased risk. The USPSTF recommends against routine BRCA counseling/testing and the policy states multigene panels and other advanced testing approaches are not medically necessary when risk-based history criteria are not met.
Use of very large multisyndrome panels may be discouraged when a targeted, syndrome-specific test is clearly indicated. Evidence and guideline reviews found minimal support for routine use of comprehensive multisyndrome panels meant for many cancer types when a focused single-syndrome test would suffice; larger panels raise VUS rates and interpretation complexity.
Given current evidence limitations, the policy considers routine clinical use of PRS for hereditary cancer risk stratification as not medically necessary. PRS may inform research or be considered adjunctive in select contexts but should not substitute for guideline-directed germline testing or be used in isolation to guide management.
The available studies on concurrent RNA testing with DNA-based panels are limited and of low quality; while RNA testing can clarify some splicing variants and may modestly increase diagnostic yield in selected series, evidence is insufficient to support broad routine concurrent RNA panel testing for all hereditary cancer DNA panels.
The policy reiterates that WES/WGS approaches for hereditary cancer identification remain unproven for routine clinical use. Although cohort studies show WES/Exome+ can detect carriers not captured by guideline-based testing, limitations in methodology, interpretation, and population representation mean routine clinical adoption is premature and such testing is listed as not medically necessary for hereditary cancer indications.
Covered Indications and Tumor-Specific Recommendations
inv-87: Germline single-gene and multigene hereditary cancer panels for individuals meeting specified personal or family history criteria, including early-onset cancers, specific tumor types, and certain tumor testing results
Single-gene and MGPT covered indications summary: Germline single‑gene testing (e.g., BRCA1/2) and multigene hereditary cancer panels are covered for individuals meeting specified personal or family history criteria, including early‑onset cancers, specified tumor types, tumor testing triggers, or family patterns described in the policy.
inv-88: Personal or family history suggestive of hereditary cancer syndromes where results will guide clinical management
Personal/family history guiding management: Personal or family history suggestive of hereditary cancer syndromes (early‑onset cancers, multiple affected relatives, syndromic features) where results will guide clinical management is an indication for testing.
inv-89: First-degree relatives of individuals with familial pancreatic cancer (FPC) for BRCA1/2 testing
Applicable Procedure and Billing Codes
Applicable procedure codesmixed
0138U
BRCA1 mRNA sequence analysis (listed example)
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)
0102U
Hereditary breast cancer-related disorders panel (17 genes)
0103U
Hereditary ovarian cancer panel (24 genes)
0129U
Hereditary breast cancer-related panel (specific genes listed)
0130U
Targeted mRNA sequence analysis panel for hereditary colon cancer (list separately)
0133U
Hereditary prostate cancer targeted mRNA panel (11 genes)
Oncology (prostate), analysis of circulating plasma proteins and germline polygenic risk score, algorithm reported as risk of likelihood of detecting clinically significant prostate cancer
81432
Hereditary breast cancer-related disorders; genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants
81435
Hereditary colon cancer-related disorders; genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants
81437
Hereditary neuroendocrine tumor-related disorders; genomic sequence analysis panel, 5 or more genes, interrogation for sequence variants and copy number variants
81441
Inherited bone marrow failure syndromes sequence analysis panel, must include sequencing of at least 30 genes (examples listed)
Rare diseases whole genome and mitochondrial DNA sequence analysis, blood or saliva
0213U
Rare diseases whole genome and mitochondrial DNA sequence analysis; identification and categorization per comparator genome
0214U
Rare diseases whole exome and mitochondrial DNA sequence analysis, proband
0215U
Rare diseases whole exome and mitochondrial DNA sequence analysis; each comparator exome
0265U
Rare constitutional and other heritable disorders whole genome and mitochondrial DNA sequence analysis, various specimen types
0266U
Unexplained constitutional or other heritable disorders tissue-specific gene expression by whole-transcriptome sequencing
81415
Exome sequence analysis (unexplained constitutional or heritable disorder)
81416
Exome sequence analysis, each comparator exome (e.g., parents, siblings)
81417
Exome re-evaluation of previously obtained exome sequence
1–10 of 13
1/2
Applicable/Added CodesCPT
0212U
Added PLA/CPT code (whole exome/genome sequencing related) as listed in Applicable Codes
0213U
Added PLA/CPT code (whole exome/genome sequencing related) as listed in Applicable Codes
0214U
Added PLA/CPT code (whole exome/genome sequencing related) as listed in Applicable Codes
0215U
Added PLA/CPT code (whole exome/genome sequencing related) as listed in Applicable Codes
0265U
Added PLA/CPT code as listed in Applicable Codes
0266U
Added PLA/CPT code as listed in Applicable Codes
81415
Added CPT code (molecular pathology/sequencing) as listed in Applicable Codes
81416
Added CPT code (molecular pathology/sequencing) as listed in Applicable Codes
81417
Added CPT code (molecular pathology/sequencing) as listed in Applicable Codes
81425
Added CPT code (multigene panel) as listed in Applicable Codes
1–10 of 12
1/2
Risk model thresholds
BRCA probability thresholdsTyrer-Cuzick, BRCAPRO, or CanRisk: ≥2.5% when the individual has a personal history of a primary solid tumor; ≥5% when the individual has no personal history of a primary solid tumor.
Lynch-predictive model thresholds (general)PREMM5, MMRpro, or MMRpredict: context-dependent thresholds; policy notes ≥2.5% in some contexts and ≥5% for selection when no personal history.
Lynch-predictive model thresholds (explicit) For Lynch syndrome evaluation, a predictive-model score ≥5% (e.g., PREMM5, MMRpro) indicates testing; for patients with CRC/EC a PREMM5 ≥2.5% may be considered for MGPT per guidance.
Operational updatesPolicy revisions replaced PENN11 with CanRisk and standardized BRCAPRO spelling in the BRCA threshold statements.
Provider Actions, Documentation, and Prior Authorization
Documentation Required
Documentation may be required
Medical records and contemporaneous documentation may be required to determine whether the member meets clinical criteria for coverage. Lack of adequate, contemporaneous medical records (including pedigree or detailed family history) may result in denial of the request. Benefit coverage is determined by the member’s benefit plan and applicable law.
Submit contemporaneous medical records with testing request.
Absence of required documentation may lead to denial per member plan.
Documentation Required
Pedigree and required clinical documentation
Submit a pedigree drawing/diagram using standardized nomenclature and contemporaneous personal and family history documentation when requesting hereditary cancer genetic testing. Documentation should include first-, second-, and third-degree relatives, ages at diagnosis or current age/age at death, primary cancer sites, bilateral disease, numbers of affected relatives, and any relevant noncancer features. Include evidence of genetic counseling discussion and informed consent where applicable.
RNA panel testing, polygenic risk scoring, and whole-exome/whole-genome sequencing for hereditary cancer indications are explicitly listed as not covered or unproven for routine clinical use when requested outside the policy’s defined indications. Requests for these modalities may require additional justification and are subject to prior authorization and review.
Routine population-wide unselected multigene testing that includes many genes with limited clinical validity or utility is considered of uncertain benefit and is not covered by the policy. Panels intended for unselected population screening lack evidence of improved outcomes and may generate uncertain findings.
Professional organizations (ACMG, USPSTF) caution against broad application of genetic testing without a clinical indication. The policy indicates panels that include genes lacking evidence to alter management are not supported and may not be covered.
Multisyndrome comprehensive panels for cancers other than the well-supported tumor types have minimal guideline support and remain investigational. Evidence reviews found limited or unclear outcome data for broad multisyndrome panel use outside defined clinical scenarios.
PRS for hereditary cancer risk assessment lacks sufficient clinical evidence and is considered investigational. While some cohort studies suggest PRS may stratify risk in select settings, overall evidence is insufficient to justify routine clinical use.
The policy states routine clinical implementation of PRS without documented counseling is not supported, and widespread concurrent RNA panel testing paired with all DNA hereditary cancer panels is unsupported by current evidence and therefore not covered for routine use.
Eligibility Requirements and Use of Tumor Testing
Eligibility for covered germline testing depends on detailed personal and family history patterns. Documentation should include first- and second-degree relatives (and when relevant third-degree), ages at diagnosis, tumor primary sites, bilateral disease, and relevant syndromic features. Coverage requires that the history meets the specific family- or personal-history criteria listed in the policy (e.g., specified numbers of affected relatives, early-age diagnoses, or predictive model thresholds).
0 top-level nodes indicated.
Coverage decisions depend on documented patterns of first- and second-degree relatives with specified cancers and on family aggregation (e.g., multiple affected relatives on the same side); absence of such documented history typically precludes coverage except where other criteria apply (tumor findings, known familial variant, or guideline-based indications).
Repeated: coverage requires detailed family history patterns including first- and second-degree relatives with early-onset or syndrome-associated cancers; these patterns determine eligibility for testing when the individual has no personal history of cancer.
Repeated: family history documentation is central to eligibility and should be used with predictive risk scores or model thresholds when applicable to establish coverage for individuals without a personal cancer history.
0 top-level nodes indicated.
0 top-level nodes indicated.
Definitions and Terminology
Primary Solid Tumor — Definition
DefinitionPrimary Solid Tumor: an abnormal mass of tissue, typically not containing cysts or liquid component, which is the original tumor in the body (excludes basal or squamous cell skin cancer).
Clinical notePrimary Solid Tumor is the tumor type referenced in policy eligibility and coverage criteria for germline testing.
Age-guideline referenceAge guideline conventions (e.g., a person is considered 45 until the day before their 46th birthday) apply to age-based criteria for primary solid tumors.
Multigene Panel — Definition
DefinitionMultigene Panel: genetic tests using next-generation sequencing to test multiple genes simultaneously; for this policy, defined as panels of five or more genes.
CPT description
Background and Evidence Summary
Hereditary cancer syndromes are caused by pathogenic germline variants (e.g., BRCA1/2, Lynch genes) that increase risk for specific primary solid tumors. Genetic testing and detailed family-history assessment help identify individuals who may benefit from targeted screening, prevention, or management changes.
Evidence supporting population-wide screening with unselected MGPT is limited. Studies show many panels include genes with low-frequency or modest associations, reducing their utility in unselected populations and supporting caution for population-based testing without clear indication.
Revision History and Policy Changes
04/01/2026policy_revisionLatest
Revised coverage criteria for multigene hereditary cancer panel testing: added serous tubal intraepithelial carcinoma and expanded renal cell carcinoma personal-history and family-history/histology criteria; updated ovarian cancer examples; replaced PENN11 with CanRisk and standardized BRCAPRO naming in BRCA probability thresholds.
04/01/2026coverage_stance_added
Added explicit not medically necessary stance that whole-exome and whole-genome sequencing for identifying hereditary cancer syndromes or syndrome risk is unproven and not medically necessary.
Policy Summary
Payersierra health and life
PolicyGenetic Testing for Hereditary Cancer
Policy CodePolicy 2026T0009TT
Change TypeCoverage criteria revisedcodes addedWES/WGS designated not medically necessary
Effective DateApr 1, 2026
Next Review DateN/A
Key ActionDocument guideline-based clinical criteria and submit contemporaneous pedigree/family-history documentation when requesting prior authorization for germline multigene panel testing.
Family history patterns such as: two or more second‑degree relatives on same side with Lynch cancers; two or more first‑ or second‑degree relatives on same side with renal cell carcinoma; at least three close blood relatives on same side with primary solid tumors; Ashkenazi Jewish ancestry plus a close relative with a BRCA‑related cancer; a family member who meets polyposis diagnostic criteria but is unwilling/unable to test; or a first‑degree relative meeting RCC genetic evaluation criteria but unwilling/unable to test.
Risk-model thresholds (no personal history): Individual has a Tyrer‑Cuzick, BRCAPRO, or CanRisk score ≥5% for BRCA1/2 pathogenic variant or a PREMM5/MMRpro/MMRpredict score ≥5% for Lynch syndrome gene mutation.
Early-onset pediatric cancer: Individuals diagnosed with cancer at age ≤18 years — multigene hereditary cancer panel testing is medically necessary.
Pancreatic cancer indications (NCCN): Personal history of exocrine or neuroendocrine pancreatic cancer, or a first‑degree relative with exocrine pancreatic cancer; neuroendocrine pancreatic tumor qualifies.
Prostate cancer indications (NCCN): Personal history of metastatic or high/very‑high risk prostate cancer or specified family/ancestry features (e.g., close relative with breast cancer ≤50, male breast cancer, ovarian/pancreatic/metastatic prostate) or ≥3 close relatives with breast/prostate on same side; unaffected individuals with a first‑degree relative meeting criteria may qualify.
Predictive model risk threshold: Predictive model estimated risk ≥5% for MMR gene P/LP variant (e.g., PREMM5, MMRpro); in some contexts a ≥2.5% threshold may be considered for selection for testing with clinical judgment.PREMM5/MMRpro >=5% (or >=2.5% in select contexts)
Tumor-identified P/LP variant: Tumor genomic testing identified a P/LP variant with potential germline implications — offer germline testing.
Laboratory and counseling support:
Genetic counseling or genetics expertise involved in ordering and interpretation; documentation of counseling and plan for cascade testing if P/LP variant found.
FPC relative BRCA1/2 testing: First‑degree relatives of individuals with familial pancreatic cancer (FPC) should be considered for BRCA1/2 testing to inform diagnostic/prognostic decisions and treatment eligibility (e.g., PARP inhibitor candidacy).
inv-90: Testing when NCCN general or tumor-specific clinical indications are met
NCCN general/tumor-specific indications: Testing when NCCN general or tumor‑specific clinical indications are met, including testing to inform systemic therapy or when a known familial P/LP variant exists, is appropriate and covered per the policy lists.
inv-91: All patients with epithelial ovarian cancer should undergo germline multigene testing including BRCA1/2 and other ovarian-susceptibility genes
Ovarian cancer—universal germline testing: All patients with epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) should undergo germline multigene testing including BRCA1/2 and other ovarian‑susceptibility genes.
inv-92: Patients with metastatic or high-risk prostate cancer and other specified prostate criteria should be offered germline testing
Prostate cancer indications: Patients with metastatic or high/very‑high risk prostate cancer and other specified prostate criteria should be offered germline testing per guideline recommendations.
inv-93: Evaluation for Lynch syndrome, adenomatous polyposis, hereditary PPGL, hereditary pancreatic or other solid-tumor predisposition when guideline criteria or tumor testing indicate possible germline variants
Evaluation for Lynch, polyposis, PPGL, pancreatic, other syndromes: Evaluation for Lynch syndrome, adenomatous polyposis, hereditary pheochromocytoma/paraganglioma (PPGL), hereditary pancreatic cancer, or other solid‑tumor predisposition is indicated when professional guideline criteria are met or tumor testing indicates possible germline variants (dMMR/MSI, tumor P/LP variant).
inv-94: Germline multigene panel testing for patients with cancer when guideline criteria are met
Panels should include strongly recommended genes: Germline multigene panel testing for patients with cancer when guideline criteria are met should include, at minimum, the more strongly recommended genes for the cancer type (e.g., BRCA1/2, MLH1, MSH2, MSH6, PMS2, EPCAM and other tumor‑specific gene lists per ASCO/NCCN).
inv-95: WES/Exome+ for identification of carriers in research/cohort contexts
WES/Exome+ in research/cohort contexts: WES/Exome+ may identify carriers of CDC Tier 1 conditions (HBOC, Lynch) in research or cohort screening contexts and can detect carriers missed by guideline‑directed testing, but methodological limitations and lack of demonstrated clinical outcomes limit routine coverage for this use.
inv-96: Multigene hereditary cancer panel testing or BRCA1/2 testing for individuals meeting personal or family history criteria
Combined personal history or family history criteria summary: Multigene hereditary cancer panel testing or BRCA1/2 testing is covered for individuals with a personal history of a primary solid tumor meeting specified tumor‑type, age, family‑history, or histology criteria, or for individuals with no personal history whose family history meets specified patterns and BRCA probability thresholds (2.5%/5% thresholds using Tyrer‑Cuzick, BRCAPRO, CanRisk; PREMM5/MMRpro/MMRpredict thresholds noted), including added RCC‑related criteria.
Minimum genes for IBMFS panel
IBMFS panel minimum gene count>= 30 genes (Inherited Bone Marrow Failure Syndrome panels must include sequencing of at least 30 genes)
Example genesExamples listed for IBMFS panels include BRCA2, BRIP1, DKC1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, GATA1, GATA2, MPL, NHP2, NOP10, PALB2, RAD51C, RPL11, RPL35A, etc.
Code linkageCPT descriptor 81441 references IBMFS panels with the ≥30-gene requirement.
Predictive model risk threshold (PREMM5/MMRpro)
Primary PREMM5/MMRpro threshold (no personal history)Predictive-model score ≥5% predicted probability of a germline MMR P/LP variant indicates testing when the individual has no personal history.
Context-specific lower thresholdSome guidance allows a lower threshold (≥2.5%) for patients with a personal history of colorectal or endometrial cancer to consider MGPT or MMR testing.
Models referencedPREMM5, MMRpro, and MMRpredict are the predictive models cited for estimating Lynch syndrome risk.
Tumor-guided considerationTumor dMMR/MSI or a tumor-detected P/LP variant may prompt germline testing regardless of model score thresholds.
Adenomatous polyposis adenoma count
Recommended testing thresholdPersonal history of ≥20 cumulative adenomas: testing is recommended.
Consider testingPersonal history of 10–19 cumulative adenomas: testing may be considered (not strictly required).
Family-history triggerFamily history of a known pathogenic variant in an adenomatous polyposis gene or affected relative meeting polyposis diagnostic criteria supports testing.
BRCA pathogenic variant probability score thresholds
BRCA probability threshold (personal history)Use Tyrer-Cuzick, BRCAPRO, or CanRisk: ≥2.5% probability of a BRCA1/2 pathogenic variant (when the individual has a personal history of a primary solid tumor).
BRCA probability threshold (no personal history)Use Tyrer-Cuzick, BRCAPRO, or CanRisk: ≥5% probability of a BRCA1/2 pathogenic variant (when the individual has no personal history of a primary solid tumor).
Updated toolsPolicy revisions replaced PENN11 with CanRisk and standardized BRCAPRO naming in these threshold statements.
Family history: first-, second-, third-degree relatives, ages at diagnosis, primary site, bilateral disease, current age/age at death.
Counseling: documentation of genetic counseling discussion and informed consent.
Documentation Required
Risk assessment documentation
When applicable, document use of validated risk assessment tools to support testing decisions (examples: BRCAPRO, BOADICEA/CanRisk, Tyrer‑Cuzick, PREMM5, MMRpro). Include the calculated score and interpretive threshold used to justify testing. For Lynch syndrome and related evaluations, document PREMM5 or other MMR predictive model scores where indicated.
List the risk model and score (e.g., PREMM5 = 5.2%).
If score meets guideline threshold, note the threshold used to justify testing.
Denial Risk
Panel selection risk and documentation
Panel selection should be tailored to the clinical question. Consider targeted single‑gene or small panels when one syndrome is most likely; consider broader multigene panels when multiple syndromes are plausible or prior testing was limited. Document the clinical rationale for the gene set selected and how results will influence medical management. Inappropriate panel choice (mismatch with clinical question or unnecessary broad panels) increases denial risk.
Provide rationale for panel size and gene content relative to phenotype and family history.
Note expected turnaround time needs when ordering larger panels.
Highlight if prior single‑gene testing was performed and why broader testing is now pursued.
Step Therapy
Stepwise testing vs upfront multigene panels
Prioritize stepwise testing when a single syndrome is most likely and rapid results are needed for treatment decision‑making; order smaller targeted panels first and larger panels later if necessary. Multigene panels may be cost‑effective when multiple syndromes are plausible or prior testing was limited, but they have higher likelihood of VUS and uncertain findings.
Stepwise vs panel: consider single‑gene or small panel first when appropriate.
If rapid results needed for treatment, order smaller targeted testing initially; larger panels can follow.
Note
Sequencing and prior testing expectations
If prior single‑gene testing (limited sequencing or without deletion/duplication analysis) was negative but clinical suspicion remains, multigene panel testing may be appropriate; document prior testing details and remaining clinical indications for broader testing.
Document prior test name, method (e.g., sequencing only), date, and results.
RNA panel testing prior authorization and limitations
Concurrent RNA panel testing (whole‑transcriptome or targeted RNA splicing panels) performed routinely with BRCA1/2 or multigene hereditary cancer panels is considered investigational/insufficient. Requests for broad concurrent RNA panels may be subject to prior authorization and/or denial. RNA testing may clarify select variants identified by DNA testing, but evidence is limited; document the specific clinical rationale if requesting concurrent RNA testing.
Concurrent RNA panels: insufficient evidence for routine use; may require prior authorization.
If RNA testing requested, provide clinical justification and prior DNA results that RNA testing is expected to clarify.
Standalone RNA panel requests without clear DNA‑variant rationale are high risk for denial.
Denial Risk
WES/WGS not medically necessary for routine hereditary cancer screening
Whole‑exome sequencing (WES) or whole‑genome sequencing (WGS) for the purpose of identifying hereditary cancer syndromes or hereditary cancer risk is considered unproven and not medically necessary for routine diagnostic assessment or population screening. Exome/genome tests have limitations (reduced CNV detection, noncoding regions not fully assessed); document these limitations and whether confirmatory testing or supplemental methods are planned.
WES/WGS: not medically necessary for routine hereditary cancer risk assessment or population screening.
If WES/WGS ordered, document limitations (CNV detection, noncoding regions) and plan for confirmatory testing if applicable.
Applicable CPT/PLA codes for exome/genome have been added to the policy's code list; verify plan‑specific PA requirements.
Billing Rule
Applicable codes added — check PA requirements
Applicable procedure codes for multigene panels, exome, and genome tests have been added to the policy and should be used for billing/reference only; inclusion does not guarantee coverage. Verify plan‑specific prior authorization requirements for these codes before ordering.
Panel and WES/WGS codes are included for reference; coverage determined by member plan and documentation.
Documentation Required
Comprehensive family history and clinical indication documentation
Comprehensive family history and documentation should be included to demonstrate how testing would benefit the individual or at‑risk relatives. For cancer predisposition testing, document how results would affect medical management, surveillance, or treatment decisions. For polyposis or Lynch syndrome evaluations, include age at diagnosis, number and relation of relatives with relevant cancers, and tumor testing results (dMMR/MSI) when available.
Document clinical indication and potential benefit to patient and family.
Include tumor testing results (e.g., dMMR/MSI) when relevant to Lynch syndrome evaluation.
For polyposis, document number/type of polyps and relevant phenotypic details.
Documentation Required
PRS counseling and documentation
When polygenic risk scores (PRS) are considered, document a provider–patient discussion about PRS limitations, ancestry‑related performance differences, and how results will be used in clinical decision‑making. Isolated PRS testing without clear clinical utility or counseling is discouraged and may be subject to denial.
Avoid ordering PRS as isolated testing without documentation of counseling and intended management changes.
Note
WES screening and population‑scale sequencing considerations
Population‑scale or screening use of whole‑exome or whole‑genome sequencing to identify hereditary cancer syndrome carriers requires further study and is not standard practice. If used outside established indications, provide strong justification, document informed consent that explains limitations/risks, and note that such uses may not be covered by the member’s plan.
WES screening: further high‑quality evidence needed before routine adoption.
If pursued, document informed consent and justification for population or screening use.
Whole-exome and whole-genome sequencing are explicitly listed as not covered for the purpose of identifying hereditary cancer syndromes or hereditary cancer syndrome risk in routine clinical practice due to unproven clinical utility and method limitations.
0 top-level nodes indicated.
Tumor tissue testing findings such as a pathogenic tumor variant with germline implications, MSI-high/dMMR by PCR/NGS/IHC, or loss of MMR proteins are referenced as triggers that should prompt germline testing per the policy; such tumor-based abnormalities can establish medical necessity for germline evaluation.
0 top-level nodes indicated.
0 top-level nodes indicated.
Reiterated: tumor testing abnormalities (pathogenic tumor variants, MSI-high, abnormal MMR IHC) are considered appropriate triggers to pursue confirmatory germline testing under the policy.
0 top-level nodes indicated.
0 top-level nodes indicated.
CPT descriptors (e.g., 81432, 81435, 81437) describe genomic sequence analysis panels of 5 or more genes interrogating sequence and copy-number variants.
Clinical useMultigene panels are an alternative to targeted single-gene selection and are commonly used when multiple syndromes are in the differential.
Multigene panel — (reiterated)
Definition (reiterated)Genomic sequence analysis panels that interrogate multiple genes simultaneously; commonly defined in this document as panels of 5 or more genes for sequence and copy-number variant detection.
Variation by testPanel composition and total number of genes analyzed vary by commercially available tests and should be chosen based on clinical context.
Interpretation implicationLarger panels may increase rates of variants of uncertain significance and require genetics expertise for interpretation.
DefinitionWhole exome/genome sequencing (WES/WGS): comprehensive sequencing approaches analyzing coding regions (exome) or the entire genome; may include mitochondrial DNA and other variant classes depending on assay.
Limitations notedStandard WES may miss CNVs, large rearrangements, and noncoding pathogenic variants; Exome+/WES has identified carriers not meeting guideline criteria but is listed as unproven for routine hereditary cancer use.
Coding examplesMultiple CPT/PLA codes (0212U–0215U, 0265U–0266U, 81415–81417, 81425–81427) are associated with WES/WGS per policy additions.
Multigene panel testing (MGPT) — Definition
DefinitionMultigene panel testing (MGPT): next-generation sequencing–based tests that evaluate multiple inherited cancer susceptibility genes simultaneously, often including full gene sequencing and deletion/duplication analysis.
Clinical guidanceMGPT should be offered with professional genetic expertise and pre/post-test counseling; panel choice must align with clinical indication.
Panel variabilityCommercial MGPT panels differ in gene content, number of genes, and turnaround time—selection is critical to clinical utility.
P/LP variant — Definition
DefinitionP/LP variant: a pathogenic or likely pathogenic germline variant associated with increased cancer risk.
Clinical implicationIdentification of a P/LP variant can influence diagnosis, management, and cascade testing for at-risk relatives.
Reporting expectationWhen a P/LP variant is found, management guidance follows consensus recommendations where available and genetic counseling is recommended.
Lynch syndrome (LS) — Definition
DefinitionLynch syndrome (LS): used when germline heterozygous P/LP variants are identified in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) or 3' EPCAM deletions.
Associated cancersLS-related cancers include colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, brain, biliary tract, small intestinal, sebaceous neoplasms, and others per guideline lists.
Testing triggersTumor dMMR (MSI-high or abnormal MMR IHC) or predictive-model scores (e.g., PREMM5/MMRpro) inform evaluation for LS.
Definition (reiterated)Germline multigene panel testing (MGPT): NGS panels analyzing multiple cancer predisposition genes simultaneously; panel composition varies by test and indication.
Testing componentsMGPT commonly includes full sequencing and deletion/duplication analysis and may be tailored to tumor type and family history.
Counseling expectationMGPT ordering should involve genetic counseling or expertise in cancer genetics due to interpretation complexity.
PRS definition — Polygenic Risk Score
DefinitionPolygenic Risk Score (PRS): a quantitative score combining the effects of multiple common genetic variants (SNPs) to estimate an individual's genetic predisposition to disease.
Evidence stanceCurrent evidence is insufficient to support routine clinical use of PRS for hereditary cancer risk assessment; PRS performance is population-dependent and should not be used in isolation.
Clinical counselingPatients considering PRS should receive documented counseling about limitations and how results may (or may not) change management.
PRS expanded definition
Expanded definitionPRS is a quantitative aggregate of many SNP effects used to estimate disease predisposition; discriminatory performance improves when combined with clinical variables and varies by derivation population.
Performance caveatModels developed in European-ancestry populations perform better in similar populations; generalizability is limited.
Clinical integrationPRS should be incorporated with clinical and family-history data if considered, but current policy treats PRS as investigational for hereditary cancer risk.
Concurrent RNA testing — Definition and purpose
DefinitionConcurrent RNA testing: assaying RNA (e.g., capture RNA-seq) alongside DNA testing to evaluate splice effects and potentially reclassify variants of uncertain significance or detect variants missed by DNA-only approaches.
Evidence summaryRNA testing can increase diagnostic yield in some studies (example: a reported 9.1% relative increase), but overall evidence quality is insufficient for routine broad adoption.
Policy stancePolicy notes concurrent RNA panel testing as unproven/insufficient for routine use; prior authorization or additional review may be applied.
Exome+ / WES — Definition
DefinitionExome+ / WES: sequencing of coding regions (exons) of the genome to identify SNVs and small indels; Exome+ may augment standard WES and has been used in cohort screening (e.g., Exome+ identified HBOC/LS carriers).
LimitationsWES/Exome+ may have reduced CNV detection and limited assessment of noncoding regions; population screening approaches require further evidence before routine adoption.
Policy stanceWhole-exome and whole-genome sequencing for identifying hereditary cancer syndromes is listed as unproven and not medically necessary for routine hereditary-cancer screening indications.
BRCA-Related Cancers — Definition (updated)
Definition referenceBRCA-Related Cancers: includes breast, ovarian (fallopian tube, primary peritoneal), pancreatic adenocarcinoma, and prostate cancer per NCCN; definition updated in policy revisions.
Policy update notePolicy revisions updated BRCA-Related Cancers definition; see definitions section for specifics.
Clinical implicationBRCA-related cancer types are used in family-history criteria and in determining eligibility for BRCA testing per model thresholds.
Lynch Syndrome-Associated Cancer — Definition (updated)
Definition referenceLynch Syndrome-Associated Cancer: includes colorectal, endometrial, gastric, ovarian, pancreatic, urothelial, brain (usually glioblastoma), biliary tract, small intestinal, sebaceous neoplasms, and keratoacanthomas (Muir-Torre features); definition updated in policy revisions.
Use in criteriaThis list of LS-associated cancers is used to define family-history and testing triggers for Lynch syndrome evaluation.
Terminology notePolicy revisions updated the Lynch Syndrome-Associated Cancer definition; refer to definitions for full list and age guides.
04/01/2026
coding_update
Added multiple CPT/PLA codes to the Applicable Codes list for WES/WGS and related sequencing panels (0212U–0215U, 0265U–0266U, 81415–81417, 81425–81427).
Note
Policy revision summary and coding additions (effective 2026-04-01)
Policy revisions effective 2026‑04‑01 added and clarified coverage criteria (including new RCC criteria) and added WES/WGS and panel CPT/PLA codes to the Applicable Codes list; verify updated PA and coding requirements in light of these material changes.
Material changes include revised RCC criteria and addition of codes 0212U–0215U, 0265U–0266U, 81415–81417, 81425–81427.