CurrentColorado Rocky Mountain Health PlansPolicy 2026T0009TT

Genetic Testing for Hereditary Cancer – Commercial and Individual Exchange Medical Policy

Defines UnitedHealthcare Commercial and Individual Exchange medical policy coverage criteria for genetic testing for hereditary cancer, including single-gene and multigene panels, populations with personal or family history of primary solid tumors, and technologies considered not medically necessary.

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyGenetic Testing for Hereditary Cancer – Commercial and Individual Exchange Medical Policy

Policy CodePolicy 2026T0009TT

Change TypeNo material change

Effective DateApr 1, 2026

Next Review DateN/A

Key ActionWhen ordering germline multigene panel testing, ensure pretest genetic counseling and that the panel is phenotype-directed and includes guideline-recommended genes; document personal and family history (pedigree) and use prior probability models when specified.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes were made in this update.

MultipleCovered Indications

Several testsNot Medically Necessary

NumerousReferenced Codes

VariesEvidence Strength

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.

Overall P/LP prevalence

Coverage Summary

Scope: This policy defines UnitedHealthcare Commercial and Individual Exchange coverage criteria for genetic testing for hereditary cancer, including single-gene testing, BRCA1/2 testing, and phenotype-directed multigene germline panels (MGPT) for individuals with a personal or family history of primary solid tumors. Effective date: April 1, 2026.

Coverage stance: The policy supports medically necessary testing when specified clinical criteria are met (e.g., BRCA1/2 testing for breast cancer diagnosed ≤ 65 years; MGPT for many tumor- and family history–based indications). It also identifies categories considered not medically necessary / unproven (see below).

High-level covered vs not-covered: Covered indications include single-gene testing and known familial-mutation testing, BRCA1/2 testing when age/history criteria are met, and multigene hereditary cancer panels when the patient meets listed tumor-based or family-history/risk-score criteria. Not medically necessary / unproven categories include concurrent RNA panels for hereditary cancer, genetic testing performed solely for polygenic risk scores (PRS), whole-exome or whole-genome sequencing to identify hereditary cancer syndromes, and broad multigene panels for indications beyond the specific covered criteria.

Key thresholds

Tyrer-Cuzick / BRCAPRO / CanRisk (personal tumor)>= 2.5% for BRCA1/2 prior probability

Tyrer-Cuzick / BRCAPRO / CanRisk (no personal history)>= 5% for BRCA1/2 prior probability

PREMM5 / MMRpro / MMRpredict (personal tumor)>= 2.5% for Lynch syndrome gene mutation probability

PREMM5 / MMRpro / MMRpredict (no personal history)>= 5% for Lynch syndrome gene mutation probability

BRCA1/2 testing — breast cancer age cutoff (BRCA-specific)Breast cancer diagnosed at age 65 years or younger

Multigene panel breast cancer age thresholdBreast cancer diagnosed at age 50 years or younger (criterion for MGPT)

Renal cell carcinoma age thresholdDiagnosed at 46 years of age or younger (triggers genetic evaluation)

Lynch syndrome age thresholdDiagnosed at 49 years or younger (often quoted as <50) for LS-related cancers

Adenomas count — recommended testing>= 20 cumulative adenomas (recommended for adenomatous polyposis testing)

Adenomas count — consider testing10–19 cumulative adenomas (testing may be considered)

Medical-Necessity Criteria (by indication)

General Coverage Rationale

Pretest genetic counseling is strongly recommended; single-gene and known familial mutation testing are proven and medically necessary.

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

Single-gene testing and known mutation testing for familial cancer are proven and medically necessary

Individuals With a Personal History of a Primary Solid Tumor - BRCA1/2

BRCA1/2 testing proven and medically necessary when specific age/history criteria are met:

BRCA1/2 gene testing is proven and medically necessary for individuals with a personal history of Breast Cancer diagnosed at age 65 years or youngerage <= 65

Coding

BRCA1/BRCA2 and Related ProceduresCPT|HCPCS|mixedCovered

0138U	BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) mRNA sequence analysis (List separately)
81162	BRCA1/BRCA2 gene analysis; full sequence analysis and full duplication/deletion analysis
81163	BRCA1/BRCA2 gene analysis; full sequence analysis
81164	BRCA1/BRCA2 gene analysis; full duplication/deletion analysis

Multi-Gene Panel / Hereditary Cancer Panel Codes (NGS panels, etc.)CPT|HCPCS|mixedCovered

0101U	Hereditary colon cancer disorders genomic sequence analysis panel (15 genes + EPCAM, GREM1)
0102U	Hereditary breast cancer-related disorders genomic sequence analysis panel (17 genes)
0103U	Hereditary ovarian cancer genomic sequence analysis panel (24 genes)
0129U	Hereditary breast cancer-related genomic sequence and deletion/duplication panel (ATM, BRCA1, BRCA2, CDH1, CHEK2, PALB2, PTEN, TP53)
0130U	Hereditary colon cancer targeted mRNA sequence analysis panel (list separately)
0133U	Hereditary prostate cancer targeted mRNA sequence analysis panel (11 genes)
0134U	Hereditary pan cancer targeted mRNA sequence analysis panel (18 genes)
0162U	Hereditary colon cancer (Lynch) targeted mRNA sequence analysis panel (MLH1, MSH2, MSH6, PMS2)
0238U	Oncology (Lynch) genomic DNA sequence analysis of MLH1, MSH2, MSH6, PMS2, EPCAM including deletions/duplications
0474U	Hereditary pan-cancer genomic sequence analysis panel of 88 genes

1–10 of 17

1/2

Whole Exome / Whole GenomeCPT|HCPCS|mixedNot Covered

0212U	Whole genome and mitochondrial DNA sequence analysis (rare diseases)
0213U	Whole genome and mitochondrial DNA sequence analysis, 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 identification of single nucleotide and copy number variants
0266U	Tissue-specific gene expression by whole-transcriptome and NGS
81415	Exome sequence analysis
81416	Exome sequence analysis, each comparator exome
81417	Re-evaluation of previously obtained exome sequence
81425	Genome sequence analysis

1–10 of 12

1/2

Genes recommended / examples in guidelines (informational)mixed

BRCA1	High-penetrance breast/ovarian cancer gene
BRCA2	High-penetrance breast/ovarian cancer gene
PALB2	Breast cancer susceptibility gene
TP53	Li-Fraumeni syndrome gene
PTEN	Cowden syndrome gene
STK11	Peutz-Jeghers syndrome gene
CDH1	Hereditary diffuse gastric cancer/breast lobular cancer gene
ATM	Associated with breast and pancreatic cancer risk
BARD1	Breast cancer associated gene
BRIP1	Ovarian cancer susceptibility gene

1–10 of 29

1/3

NCCN Panel Gene Recommendations (selected examples) - CRC-related minimummixed

APC	APC gene
MUTYH	MUTYH gene
MLH1	MLH1 gene
MSH2	MSH2 gene
MSH6	MSH6 gene
PMS2	PMS2 gene
EPCAM	EPCAM gene
BMPR1A	BMPR1A gene
SMAD4	SMAD4 gene
PTEN	PTEN gene

1–10 of 12

1/2

NCCN Panel Gene Recommendations (selected examples) - Endometrial cancer MGPT minimummixed

MLH1	MLH1 gene
MSH2	MSH2 gene
MSH6	MSH6 gene
PMS2	PMS2 gene
EPCAM	EPCAM gene
PTEN	PTEN gene
BRCA1	BRCA1 gene
BRCA2	BRCA2 gene

ASCO 'More Strongly Recommended' genes by cancer type (selected examples)mixed

BRCA1	Breast/ovarian/other - BRCA1
BRCA2	Breast/ovarian/other - BRCA2
PALB2	Breast cancer - PALB2
CDH1	Breast cancer - CDH1
PTEN	Breast cancer/Cowden - PTEN
STK11	Breast cancer - STK11
TP53	Breast cancer/sarcoma - TP53
APC	Colorectal cancer - APC
MUTYH	Colorectal cancer - MUTYH
NTHL1	Colorectal cancer - NTHL1

1–10 of 12

1/2

ASCO 'More Strongly Recommended' for specific tumors (additional examples)mixed

KIT	GIST - KIT
PDGFRA	GIST - PDGFRA
RET	Medullary thyroid carcinoma/MEN2 - RET
EGFR	NSCLC - EGFR
FH	PPGL - FH
MAX	PPGL - MAX
SDHA	PPGL - SDHA
SDHB	PPGL - SDHB
SDHC	PPGL - SDHC
SDHD	PPGL - SDHD

Provider Actions & Requirements

Prior Authorization

Testing for treatment decisions

Coverage requires prior authorization and meeting clinical criteria. Genetic testing for hereditary cancer that is intended to guide treatment decisions (e.g., therapy selection, eligibility for targeted agents or PARP inhibitors) must meet the policy's clinical criteria and be documented in the prior authorization request.

Prior authorization required when testing is requested for treatment decision-making or therapeutic selection.
Include relevant clinical details in the PA submission: tumor type, stage, prior therapies, biomarker/tumor testing results if applicable (e.g., MSI, IHC, somatic BRCA or other actionable tumor alterations).

Prior Authorization

Offer germline MGPT when indicated

Offer germline multigene panel testing (MGPT) when clinical criteria are met per this policy (personal/family history, validated probability models, tumor-to-germline signals). Panels should be selected to include genes relevant to the individual's personal and family cancer phenotype and to management/treatment implications.

Offer germline MGPT when indicated by personal history of cancer, family history meeting policy thresholds, tumor findings suggestive of a hereditary predisposition, or validated risk-model thresholds (see policy criteria).

Background & Evidence

Rationale: Hereditary cancer genetic testing is used to identify individuals with inherited variants that increase future cancer risk and to guide management for affected persons and at-risk relatives. The policy notes that approximately 5% to 10% of all cancers are hereditary, and hereditary cancers often present with earlier age at onset and autosomal dominant family patterns.

Role of family history and assessment: A detailed multigenerational family history (first–third degree) and focused clinical exam are emphasized to identify who should be tested. When applicable, the policy recommends use of validated risk models to quantify prior probability of a pathogenic variant.

Risk assessment tools: Examples of recommended models and tools cited are BRCAPRO, BOADICEA, and PREMM (PREMM5/MMRpro/MMRpredict for Lynch syndrome), which are used to determine eligibility thresholds referenced elsewhere in the policy.

Study / Source	Key finding
Whitworth et al. (2022) - breast cancer cohort	Multigene testing led to management changes in 83.8% of in-criteria and 67.6% of out-of-criteria participants with P/LP variants; two-thirds of participants with P/LP variants found testing helpful
Alvarado et al. (2020)	P/LP prevalence 11.7% among tested women; 5.4% BRCA1/2 and 6.3% non-BRCA; 55% of mutations were non-BRCA
Coughlin et al. (2022) CRC cohort	14.2% had ≥1 P/LP variant; 9.1% had CRC/polyposis-associated variants; overall clinically actionable rate ≥7.9%
Uson et al. (pancreatic cancer MGPT)	PGVs in 15.2% of participants; 68% of PGVs in BRCA1/2, PALB2, ATM, CHEK2, NBN, RAD51C; 1 in 6 participants carried a PGV
Samadder et al. (prospective universal MGPT study)	PGVs detected in 13.3% of unselected solid tumor patients; 192 clinically actionable findings not identified by guideline-based testing; treatment modified in 42 participants
Horton et al. (PPGL targeted MGPT)	P/LP in 27.5% of patients; diagnostic yield supports MGPT and universal testing in PPGL
BRCA1/2 gastric cancer association meta-analysis (de Moraes et al.)	BRCA1/2 mutations significantly associated with increased gastric cancer risk (pooled RRs reported; stronger association for BRCA2)

Definitions (policy)

Close Blood RelativesFirst-degree: parents/siblings/offspring; Second-degree: half-siblings/aunts/uncles/grandparents/grandchildren/nieces/nephews on same side; Third-degree: first cousins, great-aunts/uncles, great-grandchildren, great-grandparents on same side.

Limited Family HistoryFewer than two known first-degree or second-degree female relatives surviving beyond 45 years of age on either or both sides (e.g., adopted).

Not Medically Necessary / Unproven Uses

Not medically necessary / unproven determinations: The policy explicitly states that multigene hereditary cancer panels are unproven and not medically necessary for all indications beyond the listed covered criteria.

RNA testing: Concurrent RNA panel testing as part of hereditary cancer germline testing is considered unproven and not medically necessary for all indications; the policy cites limited and low-quality evidence and concludes more high-quality studies are needed.

Polygenic risk scores (PRS): Genetic testing performed for the purpose of calculating a polygenic risk score for hereditary cancers is considered unproven and not medically necessary due to insufficient evidence to support clinical use.

Whole-exome / whole-genome sequencing: Use of whole-exome sequencing (WES) or whole-genome sequencing (WGS) to identify hereditary cancer syndromes or hereditary cancer risk is classified as unproven and not medically necessary for that purpose in this policy.

Definitions & Terminology

Quick lookup — common definitions

Close Blood RelativesFirst-degree: parents/siblings/offspring; Second-degree: half-siblings/aunts/uncles/grandparents/grandchildren/nieces/nephews affected on same side; Third-degree: first cousins, great-aunts/uncles, great-grandchildren, great-grandparents affected on same side.

Limited Family HistoryFewer than two known first-degree or second-degree female relatives surviving beyond 45 years of age on either or both sides (i.e., individual who is adopted).

Multigene Panel / MGPTGenetic tests that use next-generation sequencing to test multiple genes simultaneously; for this policy, a multigene panel consists of five or more genes.

P/LPPathogenic or likely pathogenic variant.

VUSVariant of uncertain significance; not clinically actionable — do not change management based on VUS.

dMMR

Revision History

Policy Summary

PayerColorado Rocky Mountain Health Plans

PolicyGenetic Testing for Hereditary Cancer – Commercial and Individual Exchange Medical Policy

Policy CodePolicy 2026T0009TT

Change TypeNo material change

Effective DateApr 1, 2026

Next Review DateN/A

SourceLink

On This Page

Individuals With a Personal History of a Primary Solid Tumor - Multigene Panel Indications

Multigene hereditary cancer Panel is proven and medically necessary when individual with a Primary Solid Tumor (excluding basal or squamous cell skin cancer) meets at least one of the following:

ANY of the following

Breast Cancer diagnosed at age 50 years or youngerage <= 50
Metastatic Breast Cancer
Multiple primary Breast Cancers (prior diagnosis or bilateral primary cancer)
Triple-Negative Breast Cancer
Lobular Breast Cancer and a personal or family history of diffuse gastric cancer
Breast Cancer and Ashkenazi Jewish ancestry
Breast Cancer and individual was assigned male at birth
Breast Cancer and unknown or Limited Family History
Breast Cancer or prostate cancer and 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)
Serous tubal intraepithelial carcinoma
Pancreatic cancer
Metastatic prostate cancer
Lynch Syndrome-Associated Cancer
Neuroendocrine tumor (e.g., adrenocortical carcinoma, paraganglioma, pheochromocytoma)
Malignant phyllodes tumors
Renal cell carcinoma with any of
- Diagnosed at 46 years of age or youngerage <= 46
- Diagnosed at any age with bilateral or multifocal tumors
- Has one or more first- or second-degree relatives with renal cell carcinoma
- Has a personal or family history of mesothelioma or uveal melanoma
At least two different Primary Solid Tumors (excluding basal or squamous cell skin cancer)

Or tumor/family based features

At least one Close Blood Relative with a history of a Lynch Syndrome-Associated Cancer
At least one Close Blood Relative diagnosed with a Primary Solid Tumor at age 40 years or youngerrelative age <= 40
At least two Close Blood Relatives (in addition to affected individual) on the same side diagnosed with any Primary Solid Tumor

Individuals With No Personal History of a Primary Solid Tumor

Genetic testing (multigene panel or BRCA1/2) is proven and medically necessary when at least one of the listed family-history or risk-score criteria is met:

At least one first-degree relative with either: two or more different Primary Solid Tumors; a Lynch Syndrome-Associated Cancer; or a Neuroendocrine tumor

At least one first- or second-degree relative with any of: Breast Cancer diagnosed at age 50 years or younger; Triple-Negative Breast Cancer; Breast Cancer and relative was assigned male at birth; Metastatic prostate cancer; Ovarian Cancer; Pancreatic cancer

At least one second-degree relative with either: two or more Lynch Syndrome-Associated Cancers; or Lynch Syndrome-Associated Cancer diagnosed at age 50 years or younger

Or family/tumor patterns: Family or tumor based patterns (any of): two or more second-degree relatives same side with Lynch-associated cancer; 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 any Primary Solid Tumor; Ashkenazi Jewish ancestry plus Close Blood Relative with BRCA-Related Cancer; family member meets polyposis diagnostic criteria but is unwilling/unable to test; first-degree relative meeting renal cell criteria but unwilling/unable to test

A personal history of colorectal polyposis with at least 10 adenomasadenomas >= 10

Individual has a Tyrer-Cuzick, BRCAPRO, or CanRisk score of 5% or greater for a BRCA1/2 pathogenic variant>= 5%

Individual has a PREMM5, MMRpro, or MMRpredict score of 5% or greater for having a Lynch syndrome gene mutation>= 5%

Age-specific indication

Younger individuals with cancer

Genetic testing with a Multigene hereditary cancer Panel for individuals diagnosed with cancer at age 18 years or younger is proven and medically necessaryage <= 18

Not Medically Necessary / Unproven

Tests and uses considered unproven and not medically necessary for all indications:

Multigene hereditary cancer Panels are unproven and not medically necessary for all other indications (beyond listed covered indications)

RNA panel testing for hereditary cancers is unproven and not medically necessary for all indications

Genetic testing for the purpose of polygenic risk scoring for hereditary cancers is unproven and not medically necessary for all indications

Whole-exome and whole-genome sequencing for the purpose of identifying hereditary cancer syndromes or hereditary cancer syndrome risk is unproven and not medically necessary

General clinically indicated testing criteria (per NCCN and guideline synthesis)

Genetic testing is clinically indicated when ANY of the following general situations are present:

A patient has any blood relative with a known pathogenic/likely pathogenic (P/LP) variant in a cancer susceptibility gene.

A patient previously tested negative with limited testing and desires multigene testing.

A known P/LP variant has been identified on tumor genomic testing that has clinical implications if also identified in the germline.

Testing is performed to aid in systemic therapy and surgical decision-making.

A patient meets Li-Fraumeni syndrome, Cowden syndrome/PTEN hamartoma tumor syndrome, or Lynch syndrome testing criteria.

Breast cancer — clinically indicated testing

Testing for high-penetrance breast cancer susceptibility genes is clinically indicated when ALL of the following scenarios (any listed) apply:

Patient with breast cancer meeting one or more of the listed personal, pathology, ancestry, family, or probability criteria (diagnosed ≤50 years; used for treatment indications including PARP/olaparib; triple-negative; multiple primaries; lobular with diffuse gastric history; male sex assigned at birth; Ashkenazi Jewish ancestry; family criteria; >5% BRCA1/2 prior probability)BRCA prior probability >5% or treatment indications

Personal history at any age when used for treatment indications or PARP/olaparib: Testing will aid in treatment decisions involving PARP inhibitors in metastatic setting or adjuvant olaparib for high-risk HER2-negative disease

Breast cancer — testing may be considered

Situations where testing may be considered with counseling and management:

Personal history of breast cancer at age 65 years or younger and does not meet other criteria (moderate-penetrance genes overrepresented in older patients).age <=65

Personal history of breast cancer at any age with close relative(s) with intermediate-risk prostate cancer with intraductal/cribriform histology.

Unaffected or affected patient with 2.5% to 5% probability of BRCA1/2 P/LP variant based on models.2.5% - 5%

Personal history of malignant phyllodes tumors.

Breast cancer — low probability situations (testing not routinely recommended)

Low probability (<2.5%) that testing will identify high-penetrance genes:

Assigned female at birth, diagnosed with breast cancer > 65 years with no close relatives with breast, ovarian, pancreatic, or prostate cancer.age >65; BRCA prior probability <2.5%

Localized prostate cancer with Gleason score < 7 and no close relatives with breast, ovarian, pancreatic, or prostate cancer.Gleason <7

Consider limitations of limited family structure in those >=51 years

Ovarian cancer — clinically indicated testing

Testing for ovarian cancer susceptibility genes is clinically indicated when ANY of the following are present:

Personal history of epithelial ovarian cancer (including fallopian tube or primary peritoneal cancer) at any age

Personal history of nonepithelial ovarian cancer (sex-cord tumor with annular tubules, small cell carcinoma hypercalcemic type) at any age

Unaffected with family history: first- or second-degree relative with epithelial ovarian cancer at any age; or does not meet above but has >5% BRCA1/2 prior probability>=5%

Pancreatic cancer — clinically indicated testing

Testing for pancreatic cancer susceptibility genes is clinically indicated when ANY of the following apply:

Personal history of exocrine pancreatic cancer (including acinar cell carcinoma) or neuroendocrine pancreatic cancer

First-degree relative diagnosed with exocrine pancreatic cancer

Patient has a neuroendocrine pancreatic tumor

Prostate cancer — clinically indicated testing

Testing for prostate cancer susceptibility genes is clinically indicated when a patient has any of the following:

Tumor features: Tumor is metastatic or in the high- or very-high risk group

Ancestry/family history features (at least one close blood relative): At least one close blood relative with breast cancer age <=50; male breast cancer at any age; ovarian cancer at any age; pancreatic cancer at any age; metastatic/node-positive/high/very-high risk prostate cancer; at least three close blood relatives with breast and/or prostate cancer on same side; Ashkenazi Jewish ancestry

Patient is unaffected or affected but does not meet the above and has a first-degree blood relative who meets any of the criteria above

Prostate cancer — testing may be considered

Situations where testing for prostate cancer genes may be considered:

Diagnosed at age 55 years or younger but does not meet clinically indicated criteriaage <=55

Diagnosed with intermediate-risk prostate cancer with intraductal/cribriform histology at any age

Lynch syndrome / CRC / Endometrial / Gastric syndromes — testing criteria

Per CGA-IGC/NSGC and NCCN, evaluate for Lynch syndrome when ANY of the following apply:

Family history of a known germline MMR P/LP variant

Personal history of CRC or EC with one or more listed features: Age at diagnosis < 50 years; tumor is dMMR (MSI-high or abnormal MMR IHC); another LS-related cancer; family history of LS-related cancers in first- or second-degree relatives

Family history patterns: At least one relative diagnosed <50; at least two relatives at any age; detailed family patterns as listed (see policy)

Genetic risk model score of >=5% predicted probability of germline MMR P/LP variant (e.g., PREMM5, MMRpro)>=5%

Lynch Syndrome (LS) Testing Criteria

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

Patient has LS-related cancer and any of: Diagnosed at 49 years or younger; synchronous/metachronous LS-related cancer; first- or second-degree relative with LS-related cancer diagnosed at <=49; two or more first- or second-degree relatives with LS-related cancer

Patient has a family history of any of the following: One or more first-degree relatives with CRC or EC diagnosed <=49; one or more first- or second-degree relatives with CRC or EC and synchronous/metachronous LS-related cancer; two or more first- or second-degree relatives with LS-related cancers including one <=49; three or more relatives with LS-related cancers

Patient has a 5% or greater risk of MMR gene PV based on predictive models (e.g., PREMM5, MMRpro, MMRpredict)>=5%

Model score and special considerations: Patients with personal history of CRC/EC with PREMM5 >=2.5% should be considered for MGPT; patients with no personal history may use PREMM5 >=2.5% with clinical judgementPREMM5 >=2.5%

Personal history of a tumor with dMMR diagnosed at any age

Personal history of a P/LP variant detected on tumor genomic testing with germline implications

Adenomatous Polyposis Testing Criteria

Testing is recommended when ANY of the following are met; additional considerations may make testing reasonable:

Patient has a personal history of 20 or more cumulative adenomasadenomas >= 20

Family history of a known P/LP variant in an adenomatous polyposis gene

Patient has multifocal/bilateral congenital hypertrophy of retinal pigment epithelium

Patient has a personal history of a cribriform-morular variant of papillary thyroid cancer

Testing may be considered if any of: Desmoid tumor, hepatoblastoma, unilateral congenital hypertrophy of RPE; serrated polyposis with some adenomas; personal history of 10-19 cumulative adenomasadenomas 10-19 for consideration

Tumor-only APC variant considerations: For cancers with P/LP APC on tumor-only testing, consider germline testing if other adenomatous criteria met after reevaluation; consider germline testing for cancers diagnosed <30 years

USMSTF Recommendations for Hamartomatous Polyposis and Related Syndromes

Genetic evaluation and testing should be performed when criteria below are met:

Two or more lifetime hamartomatous polyps

A family history of hamartomatous polyps

A cancer associated with a hamartomatous polyposis syndrome in first- or second-degree relatives

Two or more histologically confirmed Peutz-Jeghers polyps

Any number of Peutz-Jeghers polyps with a family history of Peutz-Jeghers in a first-degree relative

Characteristic mucocutaneous pigmentation with a family history of Peutz-Jeghers

Five or more juvenile polyps of colon/rectum or two or more juvenile polyps elsewhere or any juvenile polyps with one or more first-degree relatives with juvenile polyposis syndrome>=5 juvenile colonic polyps or >=2 elsewhere

Patients with multiple GI hamartomas or ganglioneuromas should undergo genetic evaluation for Cowden syndrome and related conditions

Pheochromocytoma/Paraganglioma (PPGL) and Other Tumors - Testing Considerations

Testing recommendations based on guideline summaries and studies:

MGPT recommended and shows high diagnostic yield for PPGL; some authors recommend universal MGPT for PPGL regardless of features

At minimum, test for SDHB, SDHD, SDHA, VHL, SDHC, RET, MAX and consider broader panels (including FH, NF1, TMEM127, etc.)

Patients with extra-adrenal disease, early age at onset, positive family history of PPGL, and multiple tumors more likely to have PVs and should be prioritized for testing

ASCO Recommendations for Germline Testing in Patients with Cancer

When germline testing is indicated, the following should apply:

All patients with cancer should have a comprehensive family history taken and recorded

When indicated, germline testing using a multigene panel should be offered if more than one relevant gene is present; panel should at minimum include more strongly recommended genes

Smaller panels may be used initially for rapid treatment decisions, with larger panels ordered later as needed

Offer germline testing regardless of tumor testing results when patient meets germline testing criteria

ASCO — Germline testing when tumor testing reveals variants

Offer germline testing in these situations:

When tumor testing reveals a PV in listed high-impact genes (BRCA1/2, BRIP1, MLH1, MSH2, MSH6, MUTYH, PALB2, PMS2, RAD51C, RAD51D, RET, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC2, VHL), and only if patient is < 30 years of age: APC, PTEN, RB1, TP53

ASCO guidance

When tumor testing indicates a PV in ATM, BAP1, BARD1, CHEK2, DICER1, FH, FLCN, NF1, POLD1, POLE, or SDHA and only if patient is < 30 years of age CDKN2A and SMARCA4 — germline testing may be offered (or limited in a conservative approach)

ASCO guidance

NCCN Panel Gene Recommendations (selected examples)

When using germline MGPT for specific cancers, panels should include at minimum the following genes:

CRC-related panel minimum: APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM, BMPR1A, SMAD4, PTEN, STK11, TP53

Endometrial cancer panel minimum: MLH1, MSH2, MSH6, PMS2, EPCAM, PTEN, BRCA1/2

Prostate cancer panel minimum if criteria met: BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, PMS2

Pancreatic cancer panel minimum: ATM, BRCA1, BRCA2, CDK4, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53

Neuroendocrine/adrenal tumors gene set: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, MEN1, RET, CDKN1B, NF1, TSC1, TSC2, VHL

Kidney Cancer Genetic Evaluation Criteria (NCCN v1.2026)

Genetic risk evaluation and testing should be performed if ANY of the following apply:

Patient with renal cell carcinoma and any of: Diagnosed at 46 years or younger; bilateral or multifocal tumors at any age; one or more first- or second-degree relatives with renal cell carcinoma; personal or family history of mesothelioma or uveal melanoma

Tumor histology triggers: Multifocal papillary histology; hereditary leiomyomatosis-associated RCC/fumarate hydratase deficiency histology; Birt-Hogg-Dubé-related histology; angiomyolipomas plus one additional tuberous sclerosis complex criterion; succinate dehydrogenase-deficient RCC histology

Unaffected patient family history: Two or more first- or second-degree relatives on same side with RCC; first-degree relative meeting criteria for genetic evaluation but unwilling/unable to undergo testing

PRS — Policy stance

Current policy stance on PRS:

PRS is an evaluation based on many genetic variants

Evidence to support use of PRS for assessing hereditary cancer risk is currently insufficient

Document rationale for panel composition and how results will affect management or treatment; include any genes known to be associated with the phenotype.

When focused testing is appropriate (phenotype-directed single-gene or small panel), select the narrowest panel that captures clinically actionable genes for that phenotype.

Documentation Required

Pretest counseling recommended

Pretest genetic counseling is recommended prior to ordering hereditary cancer testing to ensure informed decision-making and appropriate test selection.

Document that pretest counseling occurred or that the patient was offered counseling and declined.
Include discussion of possible outcomes: pathogenic/likely pathogenic variants, variants of uncertain significance, negative results, and implications for relatives.

Documentation Required

Pedigree submission

Submission of a pedigree and detailed family history is required to support medical necessity determinations.

Provide a pedigree with ages at diagnosis and cancer types for first- and second-degree relatives when available.
If family history is limited or unknown, document reason (e.g., adoption) and any available surrogate information.

Documentation Required

Genetic counseling and informed consent

Genetic counseling and informed consent documentation should be present in the medical record prior to testing.

Document that counseling included test benefits/limitations, potential psychosocial and insurance implications, and implications for family members.
If telehealth counseling was provided, document modality and that informed consent was obtained.

Documentation Required

Use of prior probability models

When applicable, use validated prior probability models to support testing decisions and document model scores.

Examples: Tyrer-Cuzick, BRCAPRO, CanRisk for BRCA1/2 and PREMM5, MMRpro, MMRpredict for Lynch syndrome.
Include the model name, score, and threshold used to support testing in the record or PA.

Documentation Required

Interpretation and management

Document interpretation and proposed management actions following test results, including plans for cascade testing of at-risk relatives when a pathogenic/likely pathogenic variant is identified.

Document follow-up steps for positive, negative, and VUS results, and any referrals (e.g., high-risk surveillance, surgical considerations, oncology consultation).
Include whether variant findings will alter systemic therapy or eligibility for targeted treatments.

Documentation Required

Family history documentation

Record a clear family history in the medical record that supports the clinical indication for testing.

Include relationship, cancer type, age at diagnosis, and current ages or ages at death when known for relevant relatives.

Documentation Required

Tumor-to-germline reflex

When tumor testing identifies variants with possible germline relevance or shows MSI-high/loss of MMR proteins, document reflex to germline testing considerations and include tumor findings in the PA or medical record.

Provide tumor testing results (e.g., somatic NGS, MSI, IHC) that prompted consideration of germline testing.
Document whether tumor findings will lead to targeted germline MGPT.

Documentation Required

Interpretation and counseling requirement

Ensure variants are interpreted in the context of clinical management and that counseling addresses variant interpretation uncertainty.

Document that counseling included explanation of variants of uncertain significance and plan for reclassification follow-up.
Clinical decisions should not be based solely on a VUS without additional supporting evidence.

Billing Rule

Panel composition

Panel composition must be appropriate for the individual's phenotype; choose phenotype-directed panels when clinically indicated rather than broad, non-specific large panels.

When ordering a panel, document the genes included or provide the test's gene list; justify inclusion of genes that are not clearly related to the phenotype.
Phenotype-directed panels are preferred when they capture the clinically actionable genes relevant to the personal/family history; broad MGPT is appropriate when multiple syndromic possibilities exist or when prior criteria indicate MGPT.

Multigene PanelGenetic tests using next-generation sequencing to test multiple genes simultaneously; for this policy, consists of five or more genes.

P/LPPathogenic or likely pathogenic variant.

VUSVariant of uncertain significance; not clinically actionable.

MGPTGermline multigene panel testing (same as Multigene Panel definition).

dMMRMismatch repair deficiency (microsatellite instability high or abnormal MMR immunohistochemistry).

LS-related cancersColorectal, endometrial, small bowel, urothelial, ovarian, stomach, biliary, pancreatic, sebaceous, and brain (and others as listed).

Deficient mismatch repair: microsatellite instability high or abnormal MMR IHC (loss of MLH1, MSH2, MSH6, or PMS2).

LS-related cancersColorectal, endometrial, small bowel, urothelial, ovarian, stomach, biliary, pancreatic, sebaceous, and brain (usually glioblastoma) and related manifestations (per Muir-Torre).

MGPT (dup)Germline multigene panel testing (same as Multigene Panel) — included to reflect duplicated policy term definition.