CurrentCommunity Health Plan WashingtonPolicy N/A

V1.2025 Concert Genetic Testing: Hereditary Cancer Susceptibility (PDF)

Defines overview and coding implications for germline hereditary cancer susceptibility genetic testing (single-gene, targeted variant, and multi-gene panels), lists example tests, associated CPT/HCPCS codes and common ICD-10 codes for many hereditary cancer panels and single-gene analyses. This part focuses on coding implications and examples of panels/genes/tests.

Policy Summary

PayerCommunity Health Plan Washington

PolicyV1.2025 Concert Genetic Testing: Hereditary Cancer Susceptibility (PDF)

Policy CodePolicy N/A

Change TypeRevised / Added / Clarified (coding, criteria, and wording updates)

Effective Date

Next Review Date

Key ActionProviders should reference current CPT coding guidance and consult the Concert Platform for the insurer's updated policy reference-table and document clinical criteria when requesting genetic testing.

SourceLink

POLICY UPDATE CHANGES

Policy reference-table and panel/single-test listings were updated: multiple panels/tests added or removed and several CPT/HCPCS codes added/replaced (examples: added 81307, 81321, 81351; added 0162U; replaced 81403 with 81479 in many targeted tests).

'Coverage criteria' wording was replaced with 'criteria' and overview text updated to note National Society of Genetic Counselors mention.

Operational change in test naming and associated codes (81479 used instead of 81403).

Widespread coding normalization to 81479 for targeted variant analyses.

Clarifies subject of tumor profiling finding; aligning coverage trigger language.

BRCA1/2 age and probability thresholds and panel code changes in breast panel lists.

Aligns with updated NCCN and ASCO/SSO guidance; added ASCO 2024 reference.

Clarified alignment with Lynch syndrome definitions and NCCN guidance.

Expands and clarifies polyposis testing criteria and included tests.

Multiple gene-specific wording clarifications and reorganization.

Background and Rationale sections updated to reflect current guideline versions and supporting references including ASCO-SO 2024 BRCA testing guidance.

Modified panel gene/code list and removed a reviewer-facing note for ease of use.

Wording change to specify 'in the member' for clarity.

New test entry added to policy reference table.

Age limits removed where guideline rationale lacking or surveillance begins in childhood.

Replaced criteria points with a prior-probability threshold (>2.5% BRCA1/2) and simplified references.

Clinical indication expansion.

Applied to PALB2, FH, STK11, BAP1 and others to clarify tumor-to-germline confirmatory testing pathway.

Reference table expansion to include new test identifier.

Simplification/streamlining for reviewers/clients.

Panels and gene testing coverage criteria changed — may affect prior authorization determinations.

20+Genes with criteria described

MultipleCoding changes described

mRNA assaysInvestigational add-ons

0474U/0475UNew CPT tests added

NCCN/ASCO/NSGCGuideline basis

Coverage Summary & Scope

This policy defines coverage for germline hereditary cancer susceptibility testing across modalities including Targeted mutation/variant testing, single-gene sequencing, and multi-gene panels. It highlights clinical considerations (penetrance, VUS risk) and coding implications for claims submission.

The policy aligns with guideline sources (NCCN, ASCO, NSGC) and focuses on coding and insurer scope — listing example CPT/HCPCS codes and recommending providers consult the insurer's reference-table/Concert Platform for the complete, insurer-specific test-to-code mappings.

Quick eligibility thresholds

Age>= 18 years

BRCA prior probability> 2.5% based on prior probability models (TyrerCuzick, BRCApro, CanRisk)

PREMM5 (Lynch)>= 2.5% for personal history of colorectal and/or endometrial cancer

APC adenomas>= 10 cumulative adenomas

FLCN fibrofolliculomas>= 5 fibrofolliculomas/trichodiscomas with ≥1 histologically confirmed

TP53 - breast age<= 30 years (diagnosed before 31)

VHL - RCC ageRenal cell carcinoma diagnosed before age 40 years

Note on age restrictionsAge >=18 requirement removed in some gene criteria where guideline rationale or pediatric surveillance applies (e.g., FH/HLRCC)

Medical-Necessity Criteria (by panel / gene)

Overview - Indications for Testing

Covered when any of the following high‑level indications are met:

Individual meets established clinical criteria for a hereditary cancer syndrome based on personal cancer history or family history (see gene‑specific criteria below).

Testing to clarify hereditary risk when results would change medical management (surveillance, risk‑reducing interventions, targeted therapy, or eligibility for clinical trials).

Targeted germline testing to confirm a pathogenic/likely pathogenic (P/LP) variant identified by tumor profiling when the variant is in a gene with known germline cancer predisposition and confirmatory germline result would impact management or familial risk counseling.

When a known familial P/LP variant exists in a relative (targeted variant testing) — testing of the at‑risk relative is covered rather than full gene or panel testing, unless the proband meets criteria for broader testing.

Not Covered / Investigational

Investigational / Not Covered Gene- and Test-Level Statements

Render as investigational for all other indications: APC/MUTYH testing is investigational when performed for indications not explicitly covered in this policy (i.e., outside of documented criteria for hereditary colorectal/polyposis syndromes).

Render as investigational when performed as a stand-alone test: ATM and CHEK2 sequencing (full gene sequencing and deletion/duplication) are considered investigational and not covered when performed as a stand-alone test outside of the panel/criteria pathways described in this policy.

Targeted analyses investigational when criteria not met: Targeted single-variant analyses and other limited (targeted) analyses are investigational and not covered when the individual's clinical or family history meets criteria for broader testing (full gene or multi-gene panel) but only a targeted test is ordered, or when policy criteria for targeted testing are not met.

General investigational consolidation: Unless a specific covered indication and criteria are met in this policy (including gene-specific coverage statements), testing for genes not listed as covered in the applicable criteria is investigational for all other indications.

Coding — Panels, Single-Gene, and Targeted Variant Examples

Covered panel codesHCPCS|CPT|mixedCovered

0474U	GeneticsNow Comprehensive Germline Panel - pan-cancer hereditary cancer susceptibility panel (added)
81432	Multigene sequencing panel, hereditary cancer (pan-cancer)
81433	Multigene sequencing panel, hereditary cancer (pan-cancer)
81435	Hereditary colorectal cancer panel
81436	Hereditary colorectal cancer panel (larger)
81162	Hereditary breast cancer susceptibility panel example
81163	Hereditary breast cancer susceptibility panel example
81164	Hereditary breast cancer susceptibility panel example
81165	Hereditary breast cancer susceptibility panel example
81166	Hereditary breast cancer susceptibility panel example

1–10 of 20

1/2

Covered gene sequencing/deletion-duplication codesCPTCovered

81162	BRCA1/BRCA2 sequencing/deletion-duplication related (used across breast/pancreatic panels)
81163	BRCA1/BRCA2 sequencing/deletion-duplication related
81164	BRCA1/BRCA2 sequencing/deletion-duplication related
81165	BRCA1/BRCA2 sequencing/deletion-duplication related
81166	BRCA1/BRCA2 sequencing/deletion-duplication related
81167	BRCA1/BRCA2 sequencing/deletion-duplication related
81216	BRCA1/BRCA2 full analysis
81201	APC sequencing
81203	APC deletion/duplication
81406	MUTYH/other gene sequencing referenced

1–10 of 14

1/2

Targeted/known familial variant single-gene codes (examples)CPTCovered

81215	BRCA1 targeted variant or known familial variant analysis
81217	BRCA2 targeted variant or known familial variant analysis
81212	BRCA1/BRCA2 Ashkenazi Jewish 3-site founder variant analysis
81308	PALB2 targeted variant (example)
81352	TP53 targeted variant analysis
81322	PTEN targeted variant analysis
81202	APC targeted variant
81401	MUTYH targeted variant
81403	Various targeted variant analyses (historical examples)
81479	Used for many targeted variant tests (policy replacement code)

ICD-10 example groupsICD-10

Z80	Family history of primary malignant neoplasm
Z84	Family history of genetic and congenital conditions
Z85	Personal history of malignant neoplasm
C15-C26	Digestive organs neoplasms (example group)
C50	Breast cancer
C56	Ovarian cancer
C22	Liver
C45	Mesothelioma
C64	Kidney
C43	Melanoma

Replaced with 81479mixed

81479

Replaces multiple previously listed targeted variant codes (previously 81403, 81404, 81405, etc.) in many entries per policy updates

Policy-level coding changes / additionsmixed

81307	Added to Hereditary Breast Cancer Susceptibility Panels minimum gene list
81321	Added to Hereditary Breast Cancer Susceptibility Panels minimum gene list
81351	Added to Hereditary Breast Cancer Susceptibility Panels and TP53 listings
0162U	Added to Hereditary GI/Colon Cancer Panel Tests
81406	Added to MUTYH sequencing references and gastric panel lists
0157U	Added to APC sequencing/RNAInsight references (investigational when billed in addition)

Sequencing and deletion/duplication codes - policy examplesCPT|HCPCSCovered

81351	TP53 sequencing and/or deletion/duplication (listed in policy)
S3840	RET related HCPCS/Special code referenced
S3841	RB1 related HCPCS/Special code referenced
S3842	VHL related HCPCS/Special code referenced
81405	Sequencing/deletion-duplication code referenced for multiple genes

Example pancreatic/pan-cancer panel gene sequencing codesCPTCovered

81162	Panel code used in breast/pancreatic panels
81292	MLH1 related code used in panels
81295	MSH2 related code used in panels
81298	MSH6 related code used in panels
81351	TP53 sequencing used in pancreatic panels
81433	Panel code used in pancreatic panels

Neutral/explanatory: policy-level coding changesmixed

81403	Historically used targeted genomic sequence analysis code (many entries replaced by 81479)
81404	Historically used targeted sequence analysis (many entries remapped/updated)
81405	Historically used sequencing code (updated/replaced in many entries)

Covered: Targeted variant analysis codes (when criteria met)CPT|HCPCSCovered

81293	MLH1 targeted variant (example)
81296	MSH2 targeted variant (example)
81299	MSH6 targeted variant (example)
81318	PMS2 targeted variant (example)
81352	TP53 targeted variant analysis (when criteria met)
81479	Used for many targeted variant tests when criteria met (per policy)

Covered: Lynch syndrome sequencing codesCPTCovered

81292	MLH1 sequencing example
81294	MLH1 sequencing example
81295	MSH2 sequencing example
81297	MSH2 sequencing example
81298	MSH6 sequencing example
81300	MSH6 sequencing example
81317	PMS2 sequencing example
81319	PMS2 sequencing example
81403	EPCAM sequencing or other gene example

Covered: Hereditary gastric/pancreatic/polyposis gene listsCPTCovered

81201	APC sequencing included in gastric/pancreatic/polyp panels
81203	APC deletion/duplication included in panels
81406	MUTYH sequencing included in polyposis panels
81479	Other gene sequencing / unspecified multi-gene (used across panels)

Neutral: Example ICD-10 groups cited across gene panelsICD-10

Z80	Family history of primary malignant neoplasm
Z84	Family history of genetic and congenital conditions
C15-C26	Digestive organs neoplasms
C50	Breast cancer

Policy note: Use appropriate panel code when multigene panel performedmixed

No codes listed

The policy explains that many prior vendor-specific targeted variant entries were standardized and that numerous targeted variant codes have been replaced by 81479; providers should check the policy reference-table and Concert Platform for insurer-allowed test-to-code mappings.

Code lists in this document are informational only; provider_actions call out that current CPT coding guidance and the Concert Platform should be used when submitting claims and that provider billing rules and code substitutions are described in policy callouts.

Provider Actions — Authorization, Documentation & Billing

Documentation Required

Use CPT/ICD guidance and Concert Platform

Providers should follow CPT/ICD coding guidance and consult the Concert Platform or insurer reference table for the current list of registered tests when documenting and submitting genetic testing requests. The policy notes that codes in the document are informational and inclusion/exclusion does not guarantee coverage; always verify up-to-date coding before claim submission.

Documentation Required

Select appropriate test based on clinical history

Select the test modality that matches the clinical scenario—targeted known-familial variant testing, single-gene sequencing/deletion-duplication, or multi-gene panel—based on the member’s personal and family history and whether a known pathogenic/likely pathogenic familial variant exists. The policy emphasizes broader testing when clinical history warrants and that panel composition should consider gene penetrance and VUS risk.

Background, Evidence & Definitions

Germline hereditary cancer testing identifies inherited pathogenic or likely pathogenic variants that can influence screening, prevention, and treatment; testing may be performed as targeted mutation analysis, single-gene sequencing, or multi-gene panels. Panel selection should weigh gene penetrance (high vs moderate), the increased likelihood of a variant of uncertain significance (VUS) with larger panels, and the analytic/clinical validity and utility of the assay.

The National Society of Genetic Counselors endorses multi-gene panels when clinically warranted and recommends thorough evaluation of analytic/clinical validity and clinical utility; guideline-aligned testing and genetic counseling are emphasized to mitigate harms from uncertain results.

Source	Notes
NCCN guidance (multiple guidelines: Genetic/Familial High-Risk Assessment: Breast/Ovarian/Pancreatic v3.2024; Colorectal v2.2023; others)	Policy aligns criteria with NCCN recommendations (panel indications, gene lists, and tumor‑to‑germline confirmation language). References and guideline version updates cited in document.
ASCO/SSO guidance (ASCO‑SSO 2024 BRCA testing guideline, Bedrosian et al. J Clin Oncol. 2024)	ASCO/SSO recommendation used to change BRCA testing age threshold to ≤65 and incorporated into BRCA criteria and background rationale.
NSGC position statement (2017)	NSGC endorsement of multi‑gene panels when clinically warranted cited in overview; policy requires evaluation of analytic/clinical validity and utility and recommends genetic counseling involvement.
Policy reference-table / coding updates (test additions such as GeneticsNow CPT 0474U, ProstateNow 0475U, added CPTs 81307/81321/81351; replacement of many targeted codes with 81479)	Document lists numerous coding changes and additions and notes that included tests/codes are examples; advises using Concert platform for full test list and proper coding.
Guideline version update notes and rationale	Background and rationale sections updated to reflect current guideline versions and to justify criteria changes (NCCN and ASCO‑SSO references summarized).

Key definitions for ordering clinicians: Targeted mutation testing — analysis of a single known P/LP variant (used when a familial variant is known); Germline testing — testing of inherited DNA as opposed to somatic tumor testing; Close relatives — first-, second-, and third-degree blood relatives on the same side of the family as defined in the policy; VUS — variant of uncertain significance (policy notes referral to functional/research programs may be considered); Targeted Variant–Single Test (GeneDx) — operational naming convention used in the policy to denote single-site or limited targeted tests standardized across vendors; and Prior probability models — examples include Tyrer-Cuzick, BRCAPro, and CanRisk used to calculate BRCA1/2 prior-probability thresholds.

Revision History

revised

Specific vendor/test name changes (eg, added VistaSeg, Fulgent Genetics; many targeted variant entries replaced with 'Targeted Variant-Single Test (GeneDx)') and additions of RNAInsight and other panel codes.

clarified

Administrative wording changes and overview clarifications.

revised

Operational change in test naming and associated codes (81479 used instead of 81403).

Policy Summary

PayerCommunity Health Plan Washington

PolicyV1.2025 Concert Genetic Testing: Hereditary Cancer Susceptibility (PDF)

Policy CodePolicy N/A

Change TypeRevised / Added / Clarified (coding, criteria, and wording updates)

Effective Date

Next Review Date

SourceLink

On This Page

Pan‑cancer hereditary cancer susceptibility panels (0474U, 81432, 81433)

Pan‑cancer hereditary cancer susceptibility panels (e.g., CPT 81432, 81433, 0474U) are covered when ALL of the following are met:

All of the following:

(1) The individual has personal and/or family history suggestive of an inherited cancer predisposition affecting multiple organ systems (e.g., early‑onset cancers, multiple primary tumors, combinations of tumor types across family members) AND

(2) Testing results are expected to inform medical management (screening, prevention, or treatment) for the patient or at‑risk relatives AND

(3) The panel includes only genes with established clinical association to hereditary cancer susceptibility for the phenotypes under consideration and meets the minimum gene list requirement for pan‑cancer panels as defined by specialty guidelines (pan‑cancer panels should include high‑ and moderate‑penetrance genes relevant to multiple tumor types).

Note: Panels that include genes without established disease association or research‑only genes are not appropriate; consider gene‑specific testing when a single gene explains the phenotype. Maintain documentation of why a pan‑cancer panel was chosen over targeted or syndrome‑specific testing.

Hereditary GI/colorectal cancer susceptibility panels (81435, 81436, 0101U)

Hereditary GI/Colorectal cancer susceptibility panels (e.g., CPT 81435, 81436, 0101U) are covered when ALL the following are met:

Personal history of colorectal, endometrial, small‑bowel, gastric, ovarian, urothelial, or other Lynch‑associated cancers diagnosed at an age or with features suggestive of hereditary etiology OR a family history meeting guideline criteria for hereditary colorectal cancer syndromes (see Lynch and polyposis sections).

Testing results would change clinical management (surveillance, prophylactic surgery, or targeted therapy).

Panel is focused on genes with established association to colorectal/GI hereditary cancer (avoid inclusion of genes without known relevance).

APC and/or MUTYH targeted and sequencing analyses (adenomatous polyposis)

APC and/or MUTYH targeted and sequencing analyses (adenomatous polyposis) — covered when ONE of the following is met:

Individual with >10 cumulative adenomatous colorectal polyps OR

Individual with clinical diagnosis of familial adenomatous polyposis (FAP) or attenuated FAP features (hundreds to thousands of polyps or clinical diagnosis) OR

Known familial P/LP variant in APC or biallelic P/LP variants in MUTYH in a relative (targeted testing for the familial variant covered).

Note: For MUTYH, biallelic pathogenic variants explain autosomal recessive MAP; testing strategies should consider reflex to full sequencing/deletion/duplication if a single pathogenic variant is found and clinical suspicion remains high.

CDKN2A sequencing and targeted variant analysis (FAMMM / melanoma‑pancreatic cancer syndrome; 81479, 81404)

CDKN2A (FAMMM / melanoma‑pancreatic cancer syndrome) — targeted and full sequencing/deletion‑duplication coverage:

Targeted variant analysis (CPT 81479) is covered when there is a known familial P/LP CDKN2A variant in a relative.

Sequencing and/or deletion/duplication analysis (CPT 81404, 81479) is covered when ALL of the following are met:

Personal history of melanoma diagnosed <50 years OR

Personal history of ≥2 primary melanomas at any age OR

Family history meeting one of the following: (a) ≥1 first‑ or second‑degree relative with melanoma and/or pancreatic cancer; (b) ≥3 family members with melanoma and/or pancreatic cancer across at least two generations.

Note: Follow NCCN and AAD guidance for CDKN2A testing; testing is particularly warranted when family history includes pancreatic cancer or early‑onset melanomas.

SMAD4 and/or BMPR1A targeted and sequencing analyses (JPS; 81403, 81405, 81406, 81479)

SMAD4 and BMPR1A (Juvenile Polyposis Syndrome) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81403) is covered when there is a known familial P/LP variant in SMAD4 or BMPR1A.

Sequencing and/or deletion/duplication analysis (CPT 81405, 81406, 81479) is covered when ANY of the following juvenile polyposis features are present:

>5 juvenile colorectal polyps OR

Multiple juvenile polyps throughout the GI tract OR

Any number of juvenile polyps with family history of juvenile polyposis OR

Clinical findings consistent with SMAD4‑associated phenotype (e.g., juvenile polyposis with HHT features).

FH (Fumarate Hydratase) targeted and sequencing analyses (HLRCC)

FH (Fumarate Hydratase) / HLRCC — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81403) is covered when there is a known familial P/LP FH variant.

Sequencing and/or deletion/duplication analysis (relevant CPTs) is covered when ANY of the following are met:

Cutaneous leiomyomata or multiple uterine fibroids at young age (particularly in women <40) OR

Early‑onset renal cell carcinoma with histologic features suggestive of HLRCC OR

Family history consistent with HLRCC (FH P/LP variant in a relative).

Operational note: For FH targeted variant analysis, consider age of presentation — coverage supported when clinical onset is younger than typical sporadic disease and when family history raises suspicion.

TP53 targeted and sequencing analyses (Li‑Fraumeni syndrome; 81351, 81352, 81479)

TP53 (Li‑Fraumeni syndrome) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81352) is covered when a known familial P/LP TP53 variant exists.

Sequencing and/or deletion/duplication (CPT 81351, 81479) is covered when individual meets classic Li‑Fraumeni, Chompret criteria, or other NCCN/LFS indications, including:

Childhood sarcoma, premenopausal breast cancer (<31 years), adrenocortical carcinoma, brain tumor, or multiple primary tumors consistent with LFS OR

A family history meeting Chompret or classic LFS criteria per NCCN guidelines.

Note: Consider tumor‑identified TP53 variants cautiously; many somatic TP53 variants are not indicative of germline LFS — germline confirmation is appropriate when clinical/family history supports hereditary LFS.

MEN1 targeted and sequencing analyses (MEN1 syndrome; 81479, 81404, 81405)

MEN1 — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81479) covered when a known familial MEN1 P/LP variant exists.

Sequencing and/or deletion/deletion‑duplication analysis (CPT 81404, 81405) covered when individual has two or more MEN1‑associated endocrine tumors (parathyroid, pancreatic neuroendocrine, pituitary) or family history of MEN1 with affected first‑degree relative.

RET targeted and sequencing analyses (MEN2 / familial MTC; 81404, 81406, 81479, S3840)

RET (MEN2 / familial medullary thyroid carcinoma) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81404) covered for known familial RET P/LP variant.

Sequencing and/or deletion/duplication (CPT 81406, 81479, S3840) covered when ANY of the following:

Clinical or pathologic diagnosis of medullary thyroid carcinoma (MTC) OR

Primary hyperparathyroidism and MTC or family history suggestive of MEN2 OR

Family history of MTC or known RET P/LP variant in a relative.

Note: RET testing may be indicated presymptomatically in at‑risk relatives because results affect timing of prophylactic thyroidectomy.

PTCH1 / SUFU targeted and sequencing analyses (NBCCS; 81479)

PTCH1 and SUFU (NBCCS / Gorlin syndrome) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81479) is covered when a known familial P/LP variant in PTCH1 or SUFU exists.

Sequencing and/or deletion/duplication analysis (CPTs including 81479) is covered when individuals meet clinical criteria for NBCCS (e.g., multiple basal cell carcinomas, odontogenic keratocysts, palmar/plantar pits, macrocephaly, family history).

PGL/PCC - MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127 targeted and sequencing analyses

PGL/PCC genes (MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81403) covered when a known familial P/LP variant is identified in one of these genes.

Sequencing and/or deletion/duplication analysis (CPT 81404, 81405, 81406, 81479) covered when ANY of the following are present:

Paraganglioma or pheochromocytoma at any age OR

Family history of paraganglioma/pheochromocytoma OR

Tumor with biochemical or immunohistochemical features suggesting SDHx involvement (e.g., loss of SDHB IHC) .

Note: Consider NCCN/GeneReviews guidance for gene selection; testing impacts surveillance for renal and other associated tumors.

MAX/SDHx/TMEM127 sequencing and targeted analyses (gene group)

MAX/SDHx/TMEM127 targeted and sequencing analyses — gene‑specific coverage notes:

MAX/SDHx/TMEM127 targeted variant testing (81403/81479) covered when known familial P/LP variant exists.

Full sequencing/deletion/duplication (81404, 81405, 81406, 81479) covered when clinical presentation or family history indicates hereditary paraganglioma/pheochromocytoma syndrome.

STK11 targeted and sequencing analyses (Peutz‑Jeghers syndrome; 81404, 81405, 81479)

STK11 (Peutz‑Jeghers syndrome) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81479) is covered for known familial STK11 P/LP variants.

Sequencing and/or deletion/duplication (CPT 81404, 81405) covered when ANY of the following:

Multiple hamartomatous polyps or histologically confirmed Peutz‑Jeghers polyps OR

Mucocutaneous pigmented macules with a family history of PJS OR

Family history of PJS with a known STK11 P/LP variant.

VHL targeted and sequencing analyses (VHL syndrome; 81403, 81404, S3842)

VHL (Von Hippel‑Lindau syndrome) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81403) covered when there is a known familial VHL P/LP variant.

Sequencing and/or deletion/duplication analysis (CPT 81403, 81404, S3842) covered when ANY of the following:

Personal history of hemangioblastoma, clear‑cell renal cell carcinoma at young age, pheochromocytoma, or pancreatic neuroendocrine tumor suspicious for VHL OR

Family history of VHL with affected first‑degree relative or known familial VHL variant.

RB1 targeted and sequencing analyses (Retinoblastoma; 81403, 81479, S3841)

RB1 (Retinoblastoma) — targeted and sequencing/deletion‑duplication analyses:

Targeted variant analysis (CPT 81403) covered when there is a known familial RB1 P/LP variant.

Sequencing and/or deletion/duplication analysis (CPT 81479, S3841) covered when ANY of the following:

Diagnosis of retinoblastoma (unilateral or bilateral) to inform heritable status and family counseling OR

Family history of retinoblastoma in a first‑degree relative.

PALB2 sequencing and/or deletion/duplication analysis - Clinical criteria (per NCCN)

PALB2 sequencing and/or deletion/duplication analysis — clinical criteria (per NCCN):

Sequencing and/or deletion/duplication (e.g., CPTs including 81307, 81479) is covered when ANY of the following are met:

Personal history of breast cancer diagnosed at age ≤50 OR

Personal history of triple‑negative breast cancer diagnosed ≤60 OR

A personal and/or family history meeting NCCN thresholds for hereditary breast cancer testing where PALB2 testing would inform management (including increased screening, consideration of risk‑reducing strategies, or therapy selection).

Note: PALB2 may be considered in metastatic prostate cancer per guideline updates when family/personal history supports testing.

MLH1, MSH2, MSH6, PMS2, EPCAM sequencing and/or deletion/duplication analysis (Lynch syndrome)

MLH1, MSH2, MSH6, PMS2, EPCAM (Lynch syndrome) — sequencing and/or deletion/duplication analysis covered when ANY of the following are met:

Tumor demonstration of MMR deficiency (loss of MLH1, MSH2, MSH6, or PMS2 by IHC) or microsatellite instability (MSI‑high) without somatic explanation AND testing will influence management or cascade testing in family members.

Personal history meeting Lynch syndrome clinical criteria (e.g., early‑onset colorectal or endometrial cancer, multiple Lynch‑associated tumors) OR

Family history meeting Lynch syndrome criteria (Amsterdam II, revised Bethesda, or NCCN criteria) OR

PREMM5 score indicating clinically significant probability of an MLH1/MSH2/MSH6/PMS2/EPCAM germline variant per NCCN guidance (use PREMM5 thresholds consistent with NCCN recommendations).

Operational note: If tumor testing shows MLH1 loss, reflex to BRAF V600E or MLH1 promoter methylation testing to exclude sporadic MLH1 silencing is appropriate prior to germline testing.

title_extra_note":"Tumor MMR deficiency pathway: tumor‑first approaches that identify probable germline variants should be followed by confirmatory germline testing when clinical context supports hereditary risk."

BAP1 sequencing and targeted analyses — Indications (NCCN, GeneReviews)

BAP1 sequencing and deletion/duplication analysis — indications (NCCN, GeneReviews):

Sequencing and/or deletion/duplication analysis covered when ANY of the following are present:

Personal history of uveal melanoma, mesothelioma, renal cell carcinoma, or cutaneous melanoma with early onset or family history suggestive of BAP1‑TPDS OR

Family history with a known BAP1 P/LP variant (targeted testing for familial variant is covered).

PTEN sequencing and/or deletion/duplication analysis — Cowden syndrome / PHTS (NCCN)

PTEN (Cowden syndrome / PHTS) sequencing and deletion/duplication analysis — covered when ANY of the following NCCN criteria are met:

Macrocephaly with autism spectrum disorder and features suggestive of PHTS OR

Personal history of breast, thyroid (follicular), endometrial, or renal cancers with features meeting PHTS operational criteria OR

Multiple mucocutaneous lesions characteristic of Cowden syndrome OR

Family history of PTEN P/LP variant or meeting clinical diagnostic criteria for PHTS.

Targeted variant / known familial variant analyses (general rules across genes)

Gene‑specific targeted variant analysis updates and tumor→germline confirmatory rule:

Tumor profiling identified variant -> Confirmatory germline testing: Germline confirmatory testing is covered for a P/LP variant identified on somatic tumor profiling when the gene has an established germline cancer predisposition and when confirmation would impact patient management or familial risk assessment.

Gene‑specific targeted variant analysis examples (not exhaustive):

BRCA1/2, PALB2, ATM, CHEK2, TP53, BAP1, FH, MLH1/MSH2/MSH6/PMS2/EPCAM, APC, MUTYH, CDH1, CDKN2A, RET, VHL, RB1, STK11, SMAD4, BMPR1A — targeted testing for a known familial or tumor‑identified P/LP variant is appropriate when the specific variant is documented in the family or tumor and germline confirmation is indicated.

Hereditary Prostate Cancer — prior probability exception: In certain clinical scenarios (e.g., metastatic prostate cancer with strong family history or guideline‑recommended indications), gene testing may be covered despite pretest probability thresholds used elsewhere; follow NCCN and specialty guidance.

Operational notes: Maintain documentation of the familial or tumor‑identified variant (report or laboratory documentation) when ordering targeted testing; when broader testing is clinically indicated based on personal/family history, perform full gene or panel testing rather than only targeted analysis.

Not Covered / Investigational CodesCPTNot Covered

0134U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0130U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0136U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0137U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0138U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0157U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0158U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0159U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0160U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing
0161U	mRNA sequencing or RNA analysis — investigational when billed in addition to DNA testing

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mRNA sequencing (codes include, but are not limited to, 0134U, 0130U, 0136U, 0137U, 0138U, 0157U, 0158U, 0159U, 0160U, 0161U, 0162U) when billed in addition to DNA-based germline hereditary cancer testing is considered investigational and is not covered. Standalone use of these RNA/mRNA analyses or use for indications not specifically supported by the gene-specific coverage statements in this policy is investigational. Gene-specific investigational statements (for example APC and MUTYH investigational for other indications; ATM and CHEK2 sequencing investigational as standalone tests) also apply and should be followed when determining coverage.

Documentation Required

Demonstrate clinical criteria or family history

Document the specific clinical criteria, personal history, family history (degree of relation), or predictive-model score used to justify the requested test. For tumor-identified variants, include documentation that germline analysis has not yet been performed and provide the tumor profiling result and clinical rationale as part of the request.

Prior Authorization

Use appropriate panel code; Criteria-based coverage requirement

Use the appropriate panel CPT/HCPCS code on claims and for prior authorization. Coverage is criteria-based: tests billed under listed CPT/HCPCS codes must meet the gene- and syndrome-specific clinical criteria in the policy. Affected codes include: 81403, 81404, 81405, 81406, 81479, 81351, 81352, 81201, 81203, 0157U, S3840, S3841, S3842.

Use appropriate panel code on claims
Criteria-based coverage requirement
Affected codes: 81403, 81404, 81405, 81406, 81479, 81351, 81352, 81201, 81203, 0157U, S3840, S3841, S3842

Billing Rule

mRNA sequencing billed in addition is investigational

mRNA sequencing assays billed in addition to DNA testing for VUS interpretation are considered investigational and not covered when billed in addition. Do not bill the following investigational mRNA codes in addition to standard DNA testing: 0134U, 0130U, 0136U, 0137U, 0138U, 0157U, 0158U, 0159U, 0160U, 0161U, 0162U.

Investigational when billed in addition: 0134U, 0130U, 0136U, 0137U, 0138U, 0157U, 0158U, 0159U, 0160U, 0161U, 0162U

Prior Authorization

Policy coding and test-list updates require checking insurer reference table

Policy coding and available test listings are updated periodically; providers must check the insurer’s policy reference table or Concert Platform for allowed panels and single-test codes prior to submission. Examples of codes added/removed/replaced in recent updates include 81307, 81321, 81351, 0162U, 81479, 0157U, and 81406—confirm current allowance before billing.

Check insurer policy reference table for updates
Examples of codes added/removed/replaced: 81307, 81321, 81351, 0162U, 81479, 0157U, 81406

Documentation Required

Tumor-identified P/LP variants require confirmatory germline testing documentation

When a pathogenic or likely pathogenic variant is identified on tumor profiling and confirmatory germline testing is requested, attach the tumor profiling result and document the clinical rationale and why germline testing is indicated. Tumor-identified P/LP variants require evidence that germline analysis has not yet been performed and that there is reasonable clinical suspicion of germline origin.

Attach tumor profiling result
Document rationale for germline confirmation
Confirm germline testing has not yet been performed

Documentation Required

Use updated prior-probability models thresholds

Use updated prior-probability model thresholds when documenting eligibility for BRCA testing. The policy applies a >2.5% threshold (revised from >5%) based on models such as Tyrer-Cuzick, BRCApro, and CanRisk—document the model and resulting probability when used to justify testing.

Example models and threshold: Tyrer-Cuzick, BRCApro, CanRisk — BRCA prior probability >2.5%
Document model name and calculated probability

revised

Widespread coding normalization to 81479 for targeted variant analyses.

revised

Clarifies subject of tumor profiling finding; aligning coverage trigger language.

revised

Also changed BRCA1/2 age and probability thresholds and added indications per NCCN and ASCO guidance.

revised

Aligns with updated NCCN and ASCO/SSO guidance; added ASCO 2024 reference.

revised

Clarified alignment with Lynch syndrome definitions and NCCN guidance.

revised

Expands and clarifies polyposis testing criteria and included tests.

revised

Minor expansion and simplification to align with guidelines for PALB2.

revised

Reflects updated clinical diagnostic criteria and code housekeeping for PTEN.

revised

Numerous wording clarifications across many gene-specific entries (e.g., MEN1, RET, TP53, RB1, SMAD4/BMPR1A, FLCN, STK11) to better align with NCCN and other guideline language.

revised

Background and Rationale sections updated to reflect current guideline versions and supporting references including ASCO-SO 2024 BRCA testing guidance.

revised

Modified panel gene/code list and removed a reviewer-facing note for ease of use.

revised

Aligns policy with NCCN guidance (CRIT-3) and ASCO/SSO/ASCO updates; affects eligibility criteria by lowering BRCA1/2 prior-probability threshold to >2.5%.

revised

Based on updated ASCO guideline recommending BRCA1/2 testing to newly diagnosed patients age ≤65.

added

Per NCCN CRIT-3 additions: added intermediate-risk prostate cancer with intraductal/cribriform histology to BRCA-related consideration scenarios.

added

New test entry added to policy reference table: GeneticsNow Comprehensive Germline Panel (CPT 0474U).

removed

Age limits removed where guideline rationale lacking or surveillance begins in childhood (e.g., removed 'The member is 18 years or older' from multiple panels).

removed

Replaced criteria points and prior-probability thresholds for hereditary prostate cancer panels; removed some NCCN Prostate Cancer criteria points.

added

Clinical indication expansion: added metastatic prostate cancer to PALB2 criteria (reflecting PARP approvals).

revised

Applied to PALB2, FH, STK11, BAP1 and others to clarify tumor-to-germline confirmatory testing pathway (standardized 'in the member' phrasing).

revised

Reference table expansion to include new test identifier and multiple CPT/HCPCS code additions/replacements (examples: added 81307, 81321, 81351; added 0162U; replaced many targeted codes with 81479).

clarified

Non-substantive editorial streamlining with clarifying language about variant reclassification resources.

revised

Aligns policy language with updated NCCN phrasing for Ashkenazi Jewish founder BRCA testing (changed 'states that testing' to 'recommends consideration of testing').