ModifiedArizona Complete HealthPolicy N/A

Hereditary Cancer Genetic Testing (Hereditary Cancer Susceptibility Panels and Single-Gene Analyses)

Defines medical necessity, coding, and examples for germline genetic testing panels and single-gene tests for hereditary cancer susceptibility for Arizona Complete Health members. Applies to providers ordering hereditary cancer genetic testing referenced in the policy.

Policy Summary

PayerArizona Complete Health

PolicyHereditary Cancer Genetic Testing (Hereditary Cancer Susceptibility Panels and Single-Gene Analyses)

Policy CodePolicy N/A

Change TypeCriteria and coding revisionsguideline alignment

Effective DateN/A

Next Review DateN/A

Key ActionObtain and document prior authorization showing the member meets updated guideline-aligned clinical and family-history criteria before ordering panels or gene testing.

SourceLink

POLICY UPDATE CHANGES

Multiple test names, criteria points, and CPT/HCPCS codes were updated across hereditary cancer test entries.

Hereditary panel and single-gene criteria clarified and simplified for guideline alignment.

Coverage stance updated for multiple genes (example: CDKN2A sequencing changed to covered).

BRCA1/BRCA2 criteria expanded: age threshold now ≤65 and prior-probability threshold lowered to >2.5%.

Tumor-profiling-triggered germline testing phrasing standardized across gene-specific criteria.

Prostate and BRCA-related criteria updated to include intermediate-risk intraductal/cribriform histology and lower probability thresholds.

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Coverage Criteria and Medical Necessity

Pan-Cancer Hereditary Cancer Susceptibility Panels

Covered when BOTH A and B are met

A1: Personal history, or a close relative with a personal history, of breast, colorectal, or endometrial cancer diagnosed <50 years
A2: Personal history of pancreatic cancer at any age OR metastatic prostate cancer at any age
A3: Personal history of ovarian, peritoneal, or fallopian tube cancer at any age
A4: Personal or family history suspicious for more than one hereditary cancer syndrome

B: Panel includes, at a minimum, sequencing of BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PMS2

Pan-Cancer Hereditary Cancer Susceptibility Panels

Covered when BOTH of the following are met

Pan-Cancer Panel Criteria: A. Member has one of specified personal or close relative cancer histories (see subnodes); B. Panel includes minimum genes BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PMS2

A - qualifying personal/family history

A1: Personal history or close relative with breast, colorectal, or endometrial cancer diagnosed <50 years
A2: Personal history of pancreatic cancer at any age or metastatic prostate cancer at any age
A3: Personal history of ovarian, peritoneal, or fallopian tube cancer at any age

Hereditary Breast and/or Ovarian Cancer Susceptibility Panels

Covered when ALL of the following are met

Core requirements: A. Panel includes at minimum BRCA1 and BRCA2; AND B. Member meets one of the listed personal or family history criteria

Qualifying history (examples)

B1: Personal history of breast cancer diagnosed <65
B2: Personal history of ovarian, fallopian tube, or peritoneal cancer
B3: Personal history of breast cancer plus one qualifying feature (e.g., Ashkenazi Jewish ancestry; male sex assigned at birth; triple-negative breast cancer; pancreatic or ampullary cancer; metastatic or specified high-risk prostate cancer; multiple primaries; first-degree relative with early breast/ovarian/pancreatic/prostate cancer; >3 diagnoses of breast/prostate on same side of family)

Hereditary GI/Colorectal and Lynch Panels

Covered when criteria for colorectal/Lynch-related testing are met

Colorectal/Polyposis indications: Member meets findings such as ≥10 adenomatous polyps, ≥2 hamartomatous polyps, ≥5 serrated polyps proximal to rectum, or other polyposis features; OR meets adenomatous polyposis conditions per APC/MUTYH criteria

Panel gene-content requirement: Panel includes at minimum APC, MUTYH, MLH1, MSH2, MSH6, PMS2, EPCAM and may include BMPR1A, SMAD4, PTEN, STK11, TP53

Lynch sequencing indication: Lynch panel (MLH1/MSH2/MSH6/PMS2/EPCAM sequencing and/or del/dup) is indicated when: tumor shows MMR deficiency (MSI or loss of MMR protein) OR diagnosis of Lynch-related cancer with qualifying age/family features OR predictive-model risk thresholds met (eg PREMM5/MMRpro/MMRpredict)

Organ-specific hereditary cancer panels

Covered when specific age, diagnosis, or family criteria are met and panel includes minimum listed genes

Gastric panel: Member meets sequencing/del-dup clinical criteria for Lynch syndrome, hereditary diffuse gastric cancer, juvenile polyposis, Peutz-Jeghers, or APC/MUTYH conditions AND panel includes at minimum APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11

Pancreatic panel: Member has pancreatic cancer OR a first-degree relative with pancreatic cancer

Prostate panel: Member meets qualifying prostate cancer presentations (metastatic or node-positive; high/very-high risk; intermediate-risk with intraductal/cribriform histology; diagnosis ≤55) and panel includes at minimum BRCA1 and BRCA2

Neuroendocrine panel: Member has specified neuroendocrine diagnoses (eg adrenocortical carcinoma, paraganglioma/pheochromocytoma, early primary hyperparathyroidism) OR meets MEN1/RET criteria

Targeted variant / known familial variant analysis

Covered when listed familial or tumor-identified pathogenic/likely pathogenic variants are present or when ancestry-based founder testing applies

BRCA targeted/known familial variant: Member ≥18 AND a blood relative has a known BRCA1/2 P/LP variant OR a BRCA1/2 P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed

BRCA Ashkenazi founder testing: Member ≥18 AND Ashkenazi Jewish ancestry (at least one grandparent) — targeted analysis for 185delAG, 5385insC, 6174delT

PALB2/ATM/CHEK2 targeted analysis: Member ≥18 AND a close relative has a known P/LP variant in the gene OR a P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed

Lynch targeted variant analysis: Targeted analysis for MLH1, MSH2, MSH6, PMS2, EPCAM is covered when a blood relative has a known P/LP variant OR a P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed

Not-supported indications

Not supported uses: Current evidence does not support pan-cancer panels or targeted mRNA sequencing for VUS interpretation for indications other than those explicitly listed; ATM/CHEK2 sequencing as standalone is not supported

MLH1/MSH2/MSH6/PMS2/EPCAM targeted variant analysis

Targeted variant analysis for MLH1, MSH2, MSH6, PMS2, or EPCAM is covered when ANY of the following are met:

Lynch targeted: A blood relative has a known pathogenic or likely pathogenic variant in MLH1, MSH2, MSH6, PMS2, or EPCAM; OR a pathogenic or likely pathogenic variant in these genes was identified by tumor profiling in the member and germline analysis has not yet been performed.

Lynch panel sequencing and deletion/duplication

Sequencing and/or deletion/duplication analysis for Lynch panel or the specific genes is covered when ONE of the following major pathways is met:

Lynch sequencing pathways: Pathway 1: Tumor shows MMR deficiency (MSI or loss of MMR protein expression). Pathway 2: Personal diagnosis of a Lynch-related cancer AND qualifying age/family criteria (diagnosed <50, additional Lynch-related cancer, first/second-degree relative diagnosed <50, two or more relatives with Lynch-related cancers). Pathway 3: Family history meeting defined relative-based patterns or predictive-model risk thresholds (eg PREMM5 ≥2.5% for CRC/endometrial or model risk ≥5%).

APC and MUTYH testing

APC or MUTYH targeted analysis is covered when ANY of the following are met; sequencing/deletion-duplication has additional personal-history thresholds:

APC/MUTYH targeted: Targeted testing is covered if a family history of a known APC or MUTYH P/LP variant exists OR a P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

APC/MUTYH sequencing: Sequencing/del-dup is covered when member has features such as ≥10 cumulative adenomas; CHRPE; desmoid tumor; hepatoblastoma; cribriform-morular variant thyroid cancer; serrated-polyposis meeting specified counts; duodenal cancer or adenomas.

BAP1 testing

BAP1 targeted variant analysis is covered for relatives with known pathogenic variants or tumor profiling findings; sequencing/deletion-duplication analysis has detailed personal and family tumor combinations required:

BAP1 targeted: Covered if a close relative has a known BAP1 P/LP variant OR tumor profiling identified a BAP1 P/LP variant in the member and germline analysis has not yet been performed.

BAP1 sequencing: Covered when member has: (1) personal history of two or more listed BAP1-TPDS tumors (eg uveal melanoma, mesothelioma, RCC, hepatocellular carcinoma, cholangiocarcinoma, meningioma, atypical melanocytic tumors), OR (2) one listed tumor plus cutaneous melanoma or BCC, OR (3) one listed tumor plus a first/second-degree relative with listed tumors, OR similar combinatorial criteria.

FLCN (BHDS) testing

FLCN targeted testing is covered for relatives with known pathogenic variants or tumor profiling findings; sequencing/deletion-duplication analysis is covered when specific personal-history features are present:

FLCN targeted: Covered if a first- or second-degree relative has a known pathogenic FLCN variant OR tumor profiling identified a pathogenic FLCN variant in the member and germline analysis has not yet been performed.

FLCN sequencing: Covered when member has any of: ≥5 fibrofolliculomas/trichodiscomas (≥1 histologically confirmed); multiple unexplained lung cysts (± pneumothorax); renal cancer <50 years; multifocal/bilateral renal cancer; specified renal histologies; oncocytoma; angiomyolipoma; or a first-degree relative with BHDS who has not yet had genetic testing.

PTEN (Cowden syndrome / PHTS) testing

PTEN targeted testing is covered for relatives with known pathogenic variants or tumor profiling findings; sequencing/deletion-duplication analysis requires a range of personal history features or meeting clinical criteria for CS/PHTS:

PTEN targeted: Covered if a blood relative has a known PTEN P/LP variant OR tumor profiling identified a PTEN P/LP variant in the member and germline analysis has not yet been performed.

PTEN sequencing main criteria: Covered when member has BRRS, adult Lhermitte-Duclos disease, autism-spectrum disorder with macrocephaly, ≥2 biopsy-proven trichilemmomas, OR meets detailed CS/PHTS diagnostic criteria (major/minor feature combinations including macrocephaly ≥97th percentile, GI hamartomas, specific cancer/lesion counts).

CDKN2A testing

CDKN2A targeted analysis is covered for relatives with known pathogenic variants or tumor profiling findings; sequencing/deletion-duplication analysis has specific melanoma/pancreatic cancer thresholds:

CDKN2A targeted: Covered if a close relative has a known CDKN2A P/LP variant OR a CDKN2A P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

CDKN2A sequencing: Covered when member has ≥3 invasive cutaneous melanomas; OR pancreatic adenocarcinoma; OR at least one cutaneous melanoma AND ≥2 close relatives with pancreatic cancer or cutaneous melanoma on same side of family.

CDKN2A targeted variant analysis

CDKN2A targeted variant analysis is covered when ANY of the following are met:

CDKN2A targeted: A close relative has a known pathogenic or likely pathogenic CDKN2A variant OR a CDKN2A P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

CDKN2A sequencing/deletion-duplication

CDKN2A sequencing and/or deletion/duplication analysis is covered when ANY of the following are met:

CDKN2A sequencing: Member has 3 or more invasive cutaneous melanomas; OR member has pancreatic adenocarcinoma; OR member has at least one cutaneous melanoma AND at least two close relatives with pancreatic cancer or cutaneous melanoma on the same side of the family.

CDH1 targeted variant analysis

CDH1 targeted variant analysis is covered when ALL of the following are met:

CDH1 targeted: Member is 18 years or older AND (a close relative has a known CDH1 P/LP variant OR a CDH1 P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed).

CDH1 sequencing/deletion-duplication

CDH1 sequencing and/or deletion/duplication analysis is covered when ALL of the following are met:

CDH1 sequencing: Member is 18 years or older AND meets at least one listed criteria (eg diffuse gastric cancer before 50; diffuse gastric cancer with Maori ancestry; diffuse gastric cancer with personal/family cleft lip/palate; bilateral lobular breast cancer before 70; combinations of diffuse gastric and lobular breast cancer in family; two cases of gastric cancer with at least one confirmed diffuse; two cases of lobular breast cancer before 50).

SMAD4/BMPR1A targeted variant analysis

SMAD4 or BMPR1A targeted variant analysis is covered when ANY of the following are met:

SMAD4/BMPR1A targeted: A blood relative has a known pathogenic/likely pathogenic variant in SMAD4 or BMPR1A OR a P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

SMAD4/BMPR1A sequencing/deletion-duplication

SMAD4 and/or BMPR1A sequencing and/or deletion/duplication analysis is covered when ANY of the following are met:

SMAD4/BMPR1A sequencing: Member has ≥5 juvenile polyps in colon; OR multiple juvenile polyps throughout GI tract; OR a family history of juvenile polyposis syndrome.

FH targeted variant analysis

FH targeted variant analysis is covered when ANY of the following are met:

FH targeted: A first- or second-degree relative has a known FH P/LP variant OR a P/LP variant in FH was identified by tumor profiling in the member and germline analysis has not yet been performed.

FH sequencing/deletion-duplication

FH sequencing and/or deletion/duplication analysis is covered when ALL of the following are met:

FH sequencing: Member is 18 years or older AND has at least one of: cutaneous leiomyomata; uterine leiomyomata; or renal cell carcinoma.

TP53 targeted variant analysis

TP53 targeted variant analysis is covered when ANY of the following are met:

TP53 targeted: A close relative has a known TP53 P/LP variant OR a TP53 P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

TP53 sequencing/deletion-duplication (Li-Fraumeni syndrome)

TP53 sequencing and/or deletion/duplication analysis is covered when the member meets the following Li-Fraumeni–spectrum clinical criteria:

TP53 sequencing - early breast cancer: Member diagnosed with breast cancer before 31 years of age.

TP53 sequencing - pediatric leukemia: Personal or family history of pediatric hypodiploid acute lymphoblastic leukemia.

TP53 sequencing - sarcoma with family early cancer: Member diagnosed with a sarcoma before 45 years AND has a first-degree relative diagnosed with any cancer before 45 years.

TP53 sequencing - additional family criteria: Additional family or tumor-based LFS criteria (eg further relatives with cancer before 45, specific LFS tumors at any age, multiple primaries) as listed in policy.

MEN1 targeted variant analysis

MEN1 targeted variant analysis is covered when ANY of the following are met:

MEN1 targeted: A close relative has a known MEN1 P/LP variant OR a MEN1 P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

MEN1 sequencing/deletion-duplication

MEN1 sequencing and/or deletion/duplication analysis is covered when ANY of the following are met:

MEN1 sequencing: Member has personal history of at least two of: pancreatic/duodenal NET, primary hyperparathyroidism, pituitary adenoma, foregut carcinoid; OR one of these plus a close relative with at least one of above.

RET targeted variant analysis

RET targeted variant analysis is covered when ANY of the following are met:

RET targeted: A close relative has a known RET P/LP variant OR a RET P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

RET sequencing/deletion-duplication

RET sequencing and/or deletion/duplication analysis is covered when ANY of the following are met:

RET sequencing: Member has medullary thyroid cancer, adrenal pheochromocytoma, or parathyroid adenoma/hyperplasia; OR a first-degree relative meeting these criteria and not previously tested.

PTCH1/SUFU targeted variant analysis

PTCH1 or SUFU targeted variant analysis is covered when ANY of the following are met:

PTCH1/SUFU targeted: A close relative has a known PTCH1 or SUFU P/LP variant OR a PTCH1 or SUFU P/LP variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

PTCH1/SUFU sequencing/deletion-duplication

PTCH1 and/or SUFU sequencing and/or deletion/duplication analysis is covered when the member meets ONE of two pathway options:

Pathway A: Member has ≥2 major NBCCS features (eg lamellar falx calcification, jaw keratocyst, ≥2 palmar/plantar pits, >5 BCCs or BCC before 30, or a first-degree relative with NBCCS) AND at least one listed minor feature (eg childhood medulloblastoma, lympho-mesenteric/pleural cysts, macrocephaly, cleft lip/palate, vertebral/rib anomalies, polydactyly, ovarian/cardiac fibromas, ocular anomalies).

Pathway B: Member has at least one major NBCCS feature AND at least three listed minor features.

MAX/SDHx/TMEM127 targeted variant analysis

Targeted variant analysis for MAX/SDHx/TMEM127 genes is covered when ANY of the following are met:

MAX/SDHx/TMEM127 targeted: A close relative has a known pathogenic/likely pathogenic variant in MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, or TMEM127 OR a P/LP variant in any of these genes was identified by tumor profiling in the member and germline analysis has not yet been performed.

MAX/SDHx/TMEM127 sequencing/deletion-duplication

MAX/SDHx/TMEM127 sequencing and/or deletion/duplication analysis is covered when ANY of the following are met:

MAX/SDHx/TMEM127 sequencing: Member has diagnosis of pheochromocytoma, paraganglioma, clear cell RCC, or GIST; OR member has a close relative with paraganglioma or pheochromocytoma.

Targeted Variant Analysis (family/tumor-directed)

Covered when ANY one of the following is met for targeted variant analysis of the listed gene:

Targeted variant analysis indications: A close relative has a known pathogenic/likely pathogenic variant in the gene; OR a pathogenic/likely pathogenic variant was identified by tumor profiling in the member and germline analysis has not yet been performed.

Sequencing and Deletion/Duplication Analysis — Gene-specific criteria

Covered when ALL of the following for the specific gene are met (gene-specific lists below):

Gene-specific sequencing indications: Indications include diagnostic presentations or family history patterns per gene: MAX/SDH/TMEM127 for PGL/PCC/GIST/clear cell RCC; STK11 for Peutz-Jeghers features; RB1 for retinoblastoma; VHL for listed VHL-associated tumors; and others as specified in gene sections.

Multigene Panel Coverage per Professional Guidelines

Covered when panel testing is consistent with professional guidelines (examples below):

Multigene panel rationale: Multigene (pan-cancer) panels are appropriate when clinical suspicion exists for more than one hereditary cancer syndrome and panel content is tailored to phenotype; professional society guidance (NCCN, ASCO, NSGC) supports panel testing in these contexts.

Breast/ovarian panel guidance: Breast/ovarian/pancreatic/prostate panel testing recommended per NCCN/ASCO criteria (age, tumor histology, family history, and prior-probability model thresholds); include genes relevant to phenotype and consider intermediate-penetrance genes.

Colorectal/polyposis panel guidance: Colorectal/polyposis panels recommended for polyposis (≥10 adenomas) and Lynch-related presentations; include APC, BMPR1A, EPCAM, MUTYH, MLH1, MSH2, MSH6, PMS2, PTEN, SMAD4, STK11, TP53 as appropriate.

Gene/Syndrome-specific coverage criteria

Covered when ONE of the following gene- or syndrome-specific NCCN/GeneReviews-based conditions are met for the indicated test type:

Familial P/LP variant: Targeted variant testing when a blood relative has a known pathogenic/likely pathogenic variant for the gene (eg BRCA, PALB2, Lynch genes, APC/MUTYH).

Tumor-identified P/LP variant: Confirmatory germline testing when a pathogenic/likely pathogenic variant is identified on tumor genomic testing and clinical suspicion exists that it may be germline.

Syndrome-specific criteria: Syndrome-specific sequencing/del-dup indications when personal or family history meets diagnostic criteria (eg APC/MUTYH ≥20 adenomas; JPS ≥5 juvenile polyps; CDH1 combinations for diffuse gastric/lobular breast cancer; TP53 LFS/Chompret criteria; MEN1/MEN2 features).

Covered indications (per-gene and panel)

Covered when ALL of the following guideline-based conditions are met for the specified gene or test type:

Family known P/LP variant: Known familial P/LP variant: Targeted variant analysis is covered when there is a known pathogenic/likely pathogenic variant in the family for the gene in question.

Tumor profiling P/LP variant: Confirmatory germline testing is covered when tumor genomic testing identified a P/LP variant and there is reasonable clinical suspicion it may be germline.

Syndrome-specific history: Syndrome-specific personal/family history: Sequencing and/or deletion/duplication analysis is covered when individual's personal or family history meets syndrome-specific criteria as detailed in gene sections (examples: APC/MUTYH ≥20 cumulative adenomas; JPS ≥5 juvenile polyps; CDH1 diffuse gastric/lobular breast combinations; TP53 LFS criteria; MEN1/MEN2 features).

Covered indications

Covered when guideline-based indications from cited sources are met

Primary indications include: known familial pathogenic variant; tumor profiling P/LP variant with reasonable suspicion of germline origin; syndrome-specific clinical diagnostic criteria (eg MEN2, NBCCS, PGL/PCC, PJS) warranting testing.

Known familial P/LP variant: Known familial pathogenic variant: Individual has a close blood relative with a known P/LP variant in a cancer susceptibility gene.

Tumor profiling implication: Pathogenic/likely pathogenic variant identified on tumor genomic testing that has clinical implications warrants confirmatory germline testing if reasonable clinical suspicion exists.

Syndrome-specific clinical criteria: Clinical features meeting syndrome diagnostic criteria justify testing (eg MEN2 features, NBCCS major/minor criteria, PGL/PCC multiple/early-onset cases, PJS features).

Representative revised criteria groups

Policy criteria for many hereditary cancer tests were revised — examples of changes follow.

Hereditary Breast Panel changes: Hereditary Breast Panels: PALB2 removed from minimum gene list; age >=18 requirement removed in some places; code updates applied.

BRCA1/BRCA2 summary: BRCA1/BRCA2: Age threshold expanded to ≤65 for some indications; prior-probability threshold changed to >2.5%; added certain tumor histology scenarios.

CDKN2A coverage change: CDKN2A: Sequencing now covered for specified melanoma/pancreatic indications.

BRCA1/BRCA2 criteria (summary)

Coverage criteria revised or clarified for many hereditary cancer genes/panels; specific per-gene logic remains in corresponding sections.

BRCA1/BRCA2 criteria (summary): BRCA1/BRCA2 testing: Coverage expanded to include breast cancer diagnosed ≤65 and prior-probability >2.5% by models; added intermediate-risk prostate cancer with intraductal/cribriform histology as qualifying scenario.

Tumor-profiling-triggered germline testing

Covered when ALL of the following are met for targeted-variant-triggered germline testing:

Tumor-to-germline pathway: A pathogenic or likely pathogenic variant in the specified gene was identified by tumor profiling in the member AND germline analysis has not yet been performed.

Updated coverage criteria highlights

Covered when ALL of the following are met (examples reflected in document updates):

BRCA probability criterion: Member's probability of having a BRCA1/2 P/LP variant is greater than 2.5% based on prior probability models (eg Tyrer-Cuzick, BRCApro, CanRisk).

Tumor profiling confirmation: Tumor profiling P/LP variant confirmation: A P/LP variant identified by tumor profiling in the member and germline analysis has not yet been performed; confirmatory germline testing indicated when clinical suspicion of germline origin exists.

Prostate histology inclusion: Individuals with intermediate-risk prostate cancer with intraductal/cribriform histology are included as meeting criteria for BRCA consideration.

Revised Panel and Gene Criteria

Policy criteria were reorganized; multiple hereditary cancer panel criteria sets were updated or integrated.

Breast/ovarian integration: Hereditary Breast/Ovarian Panels: BRCA1/2 and PALB2 sequencing/del-dup criteria integrated; ovarian cancer added to criteria name; lobular breast cancer plus diffuse gastric cancer inclusion added; first-/second-degree relative language clarified.

Pancreatic panel revision: Pancreatic panels: Member with pancreatic cancer OR a first-degree relative with pancreatic cancer qualifies; minimum gene list removed in this section.

Pan-Cancer operational change: Pan-Cancer panels: Age ≥18 requirement removed; qualifying personal/family history criteria replaced with new A/B logic.

Specific Covered Indications by Gene/Panel

CPT/HCPCS/ICD-10 Codes and Policy Reference Table

Pan-cancer hereditary cancer susceptibility panelsmixed

81432	Hereditary cancer panel (example referenced for pan-cancer panels)
81433	Hereditary cancer panel (example referenced for pan-cancer panels)
0134U	Proprietary lab code referenced for pan-cancer panels / RNA-enhanced tests
0474U	Proprietary lab code referenced for pan-cancer panels
C15-26	ICD-10 code range referenced with pan-cancer panels
C50-58	ICD-10 code range referenced with pan-cancer panels
Z17	ICD-10 V-code referenced
Z80	Family history of primary malignant neoplasm
Z85.0-85.9	Personal history of malignant neoplasms

Hereditary breast and/or ovarian cancer panels and related codesmixed

81162	BRCA1/BRCA2 sequencing or panel code referenced for hereditary breast/ovarian panels
81166	BRCA related code referenced
81167	BRCA related code referenced
81216	BRCA2 full gene sequencing (example grouping)
81307	Gene-specific sequencing code referenced
81321	PTEN or other gene sequencing code referenced
81351	Panel-related code referenced
0129U	Proprietary lab code referenced for hereditary breast/ovarian panels
0131U	Proprietary lab code referenced
0132U	Proprietary lab code referenced

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Hereditary breast and/or ovarian cancer panels and related codesmixed

81162	BRCA1/BRCA2 sequencing or panel code referenced for hereditary breast/ovarian panels
81166	BRCA related code referenced
81167	BRCA related code referenced
81216	BRCA2 full gene sequencing (example grouping)
81307	Gene-specific sequencing code referenced
81321	PTEN or other gene sequencing code referenced
81351	Panel-related code referenced
0129U	Proprietary lab code referenced for hereditary breast/ovarian panels
0131U	Proprietary lab code referenced
0132U	Proprietary lab code referenced

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GI, gastric, pancreatic, polyposis panels and related codesmixed

81435	Hereditary GI/colon cancer panel code referenced
81436	Hereditary GI/colon cancer panel code referenced
0101U	Proprietary lab code ColoNext (Ambry) referenced
0130U	Proprietary lab code referenced
0158U	Proprietary lab code referenced for Lynch/similar panels
0159U	Proprietary lab code referenced
0160U	Proprietary lab code referenced
0161U	Proprietary lab code referenced
0162U	Proprietary lab code referenced
81201	Sequencing code referenced in gastric/polyp/pancreatic panel groups

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Single-gene, targeted variant and syndrome-specific codes (BRCA, Lynch, APC/MUTYH, PTEN, etc.)mixed

81215	BRCA targeted variant code (targeted/known familial variant)
81212	Ashkenazi Jewish founder variant BRCA panel code referenced
81308	PALB2 targeted variant code referenced
81408	Sequencing panel code referenced for ATM/CHEK2
81293	MSH6 targeted variant code referenced
81296	PMS2 targeted variant code referenced
81299	EPCAM targeted variant code referenced
81292	MLH1/MSH2/etc sequencing code referenced
81294	Sequencing/deletion-duplication code referenced
81295	Sequencing/deletion-duplication code referenced

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Sample gene-specific CPT codes (multiple genes)CPT

81403	BAP1 targeted variant analysis / other targeted analyses
81479	Unlisted molecular pathology procedure (used in multiple targeted analyses listed)

Additional gene sequencing CPT codesCPT

81322	PTEN targeted variant analysis
81321	PTEN sequencing and deletion/duplication
81404	CDKN2A sequencing and/or del/dup (panel/full gene) and other full gene sequencing codes
81406	CDH1 sequencing and/or del/dup

Sequencing and panel CPT/HCPCS codes across multiple syndromesmixed

81405	Multi-gene panel sequencing (used for SMAD4/BMPR1A, FH, TP53, RET, SDHx, etc.)
81352	TP53 targeted variant analysis
81351	TP53 sequencing and/or del/dup
81479	Unlisted molecular pathology procedure (repeated across entries)
S3840	HCPCS/other code listed with RET sequencing
S3841	HCPCS/other code listed with RB1 sequencing
S3842	HCPCS/other code listed with VHL sequencing

Selected ICD-10 codes referencedICD-10

C22	Diagnosis code listed in coding implications
Z80	Family history of primary malignant neoplasm
Z84	Family history of genetic disease
Z85	Personal history of malignant neoplasm
Z86	Personal history of other diseases

Panel coding notemixed

No codes listed

Covered CPT Codes (not specified in this segment)CPT

No codes listed

Policy reference-table CPT/HCPCS changes (excerpt)mixed

81307	appears in reference-table edits (replacement/annotation) in policy revision notes
81321	appears in reference-table edits (replacement/annotation) in policy revision notes
81351	appears in reference-table edits (replacement/annotation) in policy revision notes
0162U	referenced as added under Hereditary GI/Colon Cancer Panel Tests
81403	code noted as removed and replaced in multiple entries
81479	code used as replacement for 81403 in multiple targeted variant test entries
0235U	noted as removed from PTEN sequencing entry
0157U	added for APC sequencing with +RNAInsight
81406	listed for MUTYH full gene

Revised/Added Codes and Referencesmixed

81479	Replacement for prior 81403 in many entries
81404	Replaces 81405 for some entries (e.g., MEN2)
81307	Added to hereditary breast cancer panel minimum gene list
81321	Added to hereditary breast cancer panel minimum gene list
81351	Added to hereditary breast cancer panel minimum gene list
81433	Referenced for pancreatic cancer panels (added alongside 81351)
81406	Referenced in MUTYH full gene notes
81401	APC referenced in adenomatous polyposis conditions
81202	APC (mentioned as APC (81202) in revised title
0157U	APC + RNAInsight mention

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Added to Policy Reference TableCPT

0474U

GeneticsNow Comprehensive Germline Panel (GoPath Diagnostics)

Added to Policy Reference TableCPT

0475U

ProstateNow Prostate Germline Panel (GoPath Diagnostics)

Policy Reference Table - Added TestsCPT

0475U

ProstateNow Prostate Germline Panel (GoPath Diagnostics)

Hereditary Gastric Cancer panel gene count

Hereditary gastric cancer panel - minimum gene count6 genes (policy reference lists gene-count = 6 for hereditary gastric cancer susceptibility panels)

Example panel vendorsInvitae Gastric Cancer Panel; PreventionGenetics Gastric Cancer Panel (examples listed in coding section)

Representative CPT/code list includedExamples: 81317, 81319, 81403, 81404, 81405, 81406, 81408, 81479 (codes cited for gastric panels)

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior authorization / coding note

Prior authorization and coding: Providers must confirm prior authorization (PA) requirements and use current CPT/HCPCS panel identifiers when submitting claims. Inclusion of CPT or test names in this policy is informational only and does not guarantee coverage; verify PA rules and billing guidance on the payer platform before ordering or billing.

Use updated CPT/HCPCS codes and panel identifiers listed in the policy reference table when requesting PA (examples: 81432/81433, 0134U, 0474U, 0475U).
Inclusion or omission of specific codes in this document does not ensure coverage — check the Concert Platform (or payer portal) for registered tests and PA rules.

Prior Authorization

Prior authorization for hereditary germline testing

PA required for hereditary germline testing: Prior authorization is expected when submitting germline targeted or sequencing tests. Documentation submitted with the PA must demonstrate that the member meets the guideline- and gene/syndrome-specific medical necessity criteria described in the policy.

PA should reference the specific test/panel and the genes included; panel choice must align with the clinical presentation.

Not Medically Necessary / Not Supported

The policy cites multiple CPT and proprietary lab codes as examples but makes clear that inclusion or exclusion of any code does not guarantee coverage. Providers should confirm current coding guidance and prior-authorization requirements with the payer before ordering or billing genetic tests.

The policy states that hereditary cancer susceptibility panel targeted mRNA sequencing for interpretation of variants of unknown significance (VUS) is not supported, because such RNA analyses are typically considered quality-assurance or follow-up procedures without proven clinical utility and are not endorsed as routine coverage for VUS resolution.

Across Lynch, APC/MUTYH, and other gene sections the policy notes that mRNA sequencing analyses used solely to interpret VUS are not supported. These RNA-based tests are characterized as QA or follow‑up activities rather than established, medically necessary diagnostic procedures and therefore are not reimbursed as routine clinical testing.

For each gene-specific section the policy makes explicit that testing for the listed genes is supported only for the medically necessary indications enumerated in that section. Any use of these genes outside the specified personal- or family-history, tumor-based, or predictive-model thresholds is not supported by current evidence and therefore not covered.

The policy reiterates that testing for the named genes/syndromes is only supported when the member meets the specific personal, family, tumor, or predictive-model criteria listed. Requests that do not meet those pre-specified criteria (for targeted or sequencing/deletion-duplication analyses) are considered not supported.

Definitions and Key Terms

Genetic counseling (pre/post) definition

DefinitionPre-test and post-test genetic counseling that facilitates informed decision-making, addresses possibility of secondary/incidental findings, and a plan for returning results is strongly advised

Purpose of counselingCounseling should cover implications of testing, potential secondary findings, and management/referral options including variant reclassification programs

Recommended timingCounseling recommended both before testing (pre-test) and after results (post-test) to support informed decisions and follow-up

Pan-cancer panels definition

Pan-cancer panel definitionA multigene panel that includes genes associated with inherited susceptibility to multiple cancer types (e.g., breast, colorectal, gastric); covered when specified personal/family history criteria are met and panel includes minimum genes)

Background, Rationale, and Guideline References

Each gene-specific section includes an explicit statement that current evidence does not support testing for indications beyond those listed as medically necessary. This means requests must map to the listed clinical, family-history, tumor, or predictive-model criteria to be considered eligible for coverage.

The policy clarifies that targeted variant analyses (family- or tumor-directed) and sequencing/deletion-duplication testing for the named genes are covered only when the member meets the specific listed indications. Indications include a known familial pathogenic/likely pathogenic variant, tumor‑identified P/LP variant with pending germline analysis, syndrome-specific clinical features, or predictive-model thresholds where applicable.

Summarizing evidence limitations, the policy states that testing is not supported outside the enumerated, guideline-aligned indications. Requests that fall outside the documented per-gene or per-panel criteria risk denial because current evidence does not demonstrate clinical utility for those uses.

The document reiterates that ATM and CHEK2 are lower-penetrance genes relative to high-penetrance breast cancer genes; without gene-specific clinical criteria, standalone sequencing of these genes may be unsupported and should not be requested as first-line testing absent qualifying clinical or family-history indications.

The policy references ASCO's position that it can be appropriate to exclude certain polyposis-related genes from multigene panels when the patient's phenotype or family history is not consistent with those conditions, reinforcing a phenotype-driven selection of genes on panels.

Policy Update Changes

2024-04-24policy_update

Policy updated to V2.2024: coding tables and policy criteria revised with semi-annual review; vendor/test name standardization and multiple operational changes (e.g., replacement of 81403 with 81479; addition of codes 81307, 81321, 81351 to some panels).

2024-04-24coding_change

Policy reference-table CPT/HCPCS edits: 81403 replaced with 81479 in multiple entries; other code adjustments and additions noted (examples in reference-table excerpt).

2024-04-24

Policy Summary

PayerArizona Complete Health

PolicyHereditary Cancer Genetic Testing (Hereditary Cancer Susceptibility Panels and Single-Gene Analyses)

Policy CodePolicy N/A

Change TypeCriteria and coding revisionsguideline alignment

Effective DateN/A

Next Review DateN/A

Key ActionObtain and document prior authorization showing the member meets updated guideline-aligned clinical and family-history criteria before ordering panels or gene testing.

SourceLink

On This Page

PREMM5 threshold (used for Lynch assessment)

PREMM5 score definitionPREMM5 is a predictive model estimating probability of carrying an MMR gene pathogenic variant used to determine Lynch syndrome testing eligibility

PREMM5 threshold examplesPolicy cites PREMM5 ≥2.5% for individuals with personal history of colorectal and/or endometrial cancer; also notes model-based risk ≥5% for Lynch panel consideration

Model names referencedExamples of predictive models cited: PREMM5, MMRpro, MMRpredict (used to support Lynch sequencing indications)

Prior Authorization

Prior authorization for targeted variant confirmation or germline testing

Targeted variant confirmation / germline testing PA: Prior authorization is required for targeted variant testing requested to confirm a known familial variant or a tumor-identified pathogenic/likely pathogenic (P/LP) variant. Documentation must show the familial or tumor result and clinical justification for germline confirmation.

If a tumor profiling result identified a P/LP variant, include the tumor report and rationale supporting the likelihood the variant is germline.
For known familial variants, include documentation of the relative's test result and relationship to the member.

Prior Authorization

Prior authorization aligned to guideline criteria

PA aligned to guideline criteria and clinical indication: Prior authorization requests should explicitly map the member's personal and family history and clinical features to the guideline-based indications in the policy. Tests that do not meet the listed criteria may be denied.

Examples of guideline-aligned expectations: Lynch criteria (MMR deficiency, PREMM5/MMRpro score ≥ thresholds), BRCA criteria (breast cancer ≤65 or prior-probability >2.5%), adenomatous polyposis criteria (≥20 adenomas).
When ordering a panel because overlapping phenotypes are suspected, document why a multigene panel is preferred over single-gene testing.

Documentation Required

Document family history/clinical features

Document family history and clinical features: PA and medical record documentation must include relevant personal and family history, mapping to the policy criteria. Lack of adequate documentation increases the risk the request will be denied.

Provide ages at diagnosis, primary tumor types, degree of relation, and prior probability model scores when applicable (e.g., Tyrer-Cuzick, BRCAPro, CanRisk, PREMM5).
For RB1, STK11, CDH1 and other gene-specific indications, include the diagnosis details, histology, and any tumor profiling results that prompted germline testing.

Billing Rule

Use updated codes and panel identifiers; new policy reference table tests and affected codes

Updated codes, reference-table tests, and policy changes: Use the revised policy reference table and newly added tests/panel identifiers when requesting PA. Newly added tests (examples) may require PA under the updated criteria.

New/renamed tests added to the reference table (examples: GeneticsNow Comprehensive Germline Panel 0474U; ProstateNow 0475U) should be used when applicable.
Policy edits replaced some legacy single-test CPTs (e.g., 81403) with current mapping (e.g., 81479) — confirm the current code mapping for the laboratory test before submission.

Denial Risk

Prior authorization requires documentation of updated clinical criteria; indication-based denial risk

Documentation expectations and denial risk: Prior authorization requires documentation of updated clinical criteria and clear clinical rationale. Tests ordered outside the policy’s medically necessary indications, or without supporting documentation, are at increased risk for denial.

Pan-cancer panels must meet BOTH required criteria A and B in the pan-cancer section; ordering a pan-cancer panel without meeting BOTH criteria may be denied.
Breast/ovarian panels must include at minimum BRCA1/2 and the member must meet qualifying criteria; panels lacking required genes or clinical concordance risk denial.

Documentation Required

Confirmatory germline testing when tumor profiling finds P/LP variant(s)

Tumor profiling and confirmatory germline testing: When germline testing is requested because of a tumor-identified P/LP variant, the PA must include the tumor profiling report and a clinical rationale showing reasonable suspicion the variant is germline. Absence of clinical suspicion may not justify germline testing.

Include tumor genomic report with the P/LP variant annotation, tumor site, and any relevant IHC/MSI results that support consideration of germline origin.
If confirmatory germline testing is requested, document why the variant is likely germline (family history, variant type, tumor-normal considerations).

Note

Guideline-based indication expectation; use targeted testing when appropriate; prefer panels for overlapping phenotypes; VUS follow-up

Test selection guidance and operational preferences: Prefer targeted testing when a known familial or tumor-identified variant is present; prefer multigene panel testing when multiple syndromes or overlapping phenotypes are suspected. Consider additional evaluation for variants of uncertain significance (VUS) such as RNA studies or referral to research/variant reclassification programs.

When a familial/tumor variant is known, order targeted single-variant testing rather than broad sequencing unless criteria indicate otherwise.
When multiple genes could explain the phenotype, order a clinically directed multigene panel that includes relevant genes; document why panel selection fits the clinical picture.
For VUS results, document consideration of RNA testing or research reclassification pathways before using results to guide clinical management.

Pan-cancer hereditary cancer susceptibility panel — definition

Hereditary pan-cancer hereditary cancer susceptibility panel — definitionIntegrated multigene panel that includes genes associated with inherited risk across multiple cancers; policy requires panel to include, at minimum, BRCA1, BRCA2, EPCAM, MLH1, MSH2, MSH6, PMS2 when used as a pan-cancer panel

Coverage linkageCoverage requires BOTH: qualifying personal/family history AND panel gene content meeting the minimum gene-list requirement

Examples of useAppropriate when individual or family history suggests more than one hereditary cancer syndrome; professional guidelines recommend phenotype-directed panel selection

Targeted testing definition

Targeted testing definitionGermline testing that looks specifically for a known pathogenic or likely pathogenic familial variant (single-site analysis) rather than full gene sequencing; appropriate when a familial variant is known or tumor profiling identified a P/LP variant and germline testing not yet performed

Appropriate scenariosUsed for known familial variants (first-/second-degree relative) or tumor-identified P/LP variants pending germline confirmation

Contrast to sequencingTargeted testing is narrower and generally less costly than sequencing/deletion-duplication analysis and is the preferred approach when a specific familial variant is established

Pan-cancer panel description and med necessity context

Panel description and medical necessity contextPan-cancer panels analyze a set of genes associated with multiple cancer phenotypes; medically necessary when member meets qualifying personal/family history AND the panel includes required minimum genes (BRCA1/BRCA2 and Lynch genes)

Professional guidanceNCCN, NSGC, and ASCO support multigene panels when clinically warranted; panel selection should consider gene content and clinical utility

Coding/noteIf a multigene panel is performed, the appropriate panel billing code should be used (policy coding guidance provided)

Targeted variant analysis definition

Targeted variant analysis definitionGermline testing that looks specifically for a known pathogenic or likely pathogenic variant identified in a relative or by tumor profiling (single-site/single-variant analysis)

When to useIndicated when a close relative has a known pathogenic variant or when tumor profiling identified a P/LP variant and germline testing has not yet been performed

Coding implicationTargeted analyses typically billed with single-site/targeted variant codes; policy provides standardized naming (Targeted Variant - Single Test)

Sequencing and/or deletion/duplication analysis definition

Sequencing and/or deletion/duplication analysis definitionComprehensive gene analysis including sequencing and copy-number (deletion/duplication) assessment used when personal/family history meets syndrome-specific criteria

When indicatedUsed when member meets diagnostic or family-history thresholds requiring full gene analysis (e.g., polyposis, classic LFS criteria, CDH1 criteria)

Panel vs single-geneMay be performed as gene-specific sequencing or as part of a multigene panel depending on phenotype and guideline recommendations

Multigene (pan-cancer) panel definition

Multigene (pan-cancer) panel definitionAnalysis of a set of genes associated with one or more cancer phenotypes in a family; may include intermediate-penetrance genes and is appropriate when suspicion exists for multiple hereditary syndromes

Clinical guidanceNCCN and ASCO endorse multigene panels when clinically warranted; panel gene content should be selected based on phenotype and family history

Billing noteIf a multigene panel is performed, use the appropriate panel billing code per policy coding guidance

Tumor-identified P/LP variant definition

Tumor-identified P/LP variant definitionA pathogenic or likely pathogenic variant found on tumor genomic profiling that could represent a germline variant and, if confirmed in the germline, would affect cancer risk or management

Policy actionConfirmatory germline testing is indicated when tumor profiling identifies a P/LP variant and there is reasonable clinical suspicion of germline origin

Standardized wordingPolicy standardizes phrasing: 'A pathogenic or likely pathogenic variant in [gene] was identified by tumor profiling in the member and germline analysis has not yet been performed.'

Multigene panel testing definition

Multigene panel testing definitionGermline testing that assesses multiple cancer susceptibility genes simultaneously; recommended when suspicion exists for more than one gene related to the cancer phenotype

Professional endorsementNCCN, NSGC, and ASCO guidance support use of multigene panels when clinically appropriate; consider gene content, analytic validity, and clinical utility before ordering

VUS managementPost-test counseling should consider referral to variant reclassification programs or research to clarify VUSs

Close relatives definition (first-, second-, third-degree)

Close relatives definitionIncludes first-, second-, and third-degree blood relatives (first-degree: parents, siblings, children; second-degree: grandparents, aunts/uncles, nieces/nephews, grandchildren, half-siblings; third-degree: great grandparents/aunts/uncles, first cousins)

Use in family-history criteriaPolicy frequently references first- or second-degree relatives when specifying qualifying family-history requirements for testing

Implication for targeted testingKnown pathogenic variant in a close relative (degree as specified) supports targeted familial variant analysis

Lynch syndrome–related cancer definition (list of tumor types)

Lynch syndrome–related cancer definitionIncludes colorectal, endometrial, gastric, ovarian, pancreatic, ureter and renal pelvic, brain (usually glioblastoma), biliary tract, small intestinal, sebaceous adenoma/carcinoma, or keratoacanthoma

Use in criteriaThese tumor types are used to define Lynch-associated personal or family history indications for Lynch panel testing

Policy cross-referenceAppears in Lynch sequencing and targeted variant analysis sections to determine eligibility pathways

Tumor-profiling-triggered germline testing definition

Tumor-profiling-triggered germline testing definitionGermline testing considered when a pathogenic or likely pathogenic variant is identified on tumor genomic profiling in the member and germline analysis has not yet been performed

Standardized phrasingPolicy uses uniform wording across many targeted variant sections: 'A pathogenic or likely pathogenic variant in [gene] was identified by tumor profiling in the member and germline analysis has not yet been performed.'

Documentation requirementRequests should document the tumor profiling result and clinical justification that the variant could be germline

Tumor-profile prompted germline testing standardized phrase

Tumor-profile prompted germline testing standardized phrase'A pathogenic or likely pathogenic variant identified by tumor profiling in the member and germline analysis has not yet been performed' — standardized across policy for tumor-prompted germline testing

Use caseApplied when tumor genomic testing identifies a P/LP variant and germline testing has not yet occurred; confirmatory germline testing covered when clinical suspicion exists

Evidence/documentationPolicy requires documentation of tumor profiling result and rationale for germline confirmation when submitting requests

Hereditary Breast and/or Ovarian Cancer Susceptibility Panels integrated criteria description

Integrated hereditary breast/ovarian panel descriptionHereditary Breast and/or Ovarian Cancer Susceptibility Panels now integrate BRCA1/2 and PALB2 sequencing/deletion-duplication criteria and include ovarian cancer in the criteria name

Minimum gene requirementPanel must include at minimum BRCA1 and BRCA2 for hereditary breast/ovarian panel coverage (PALB2 removed from minimum gene-list to reduce redundancy)

Age/family-history triggersIncludes age-based triggers such as breast cancer diagnosed ≤65 and family-history permutations (first- or second-degree relatives) in updated criteria