Centene genetic testing coverage & prior auth

Coverage Criteria for Genetic Testing in Gastroenterology

Known Familial Variant Analysis

Targeted mutation analysis for a known familial variant (81403) is considered medically necessary when ALL of the following are met

Known familial variant criteria: Member/enrollee has a close relative with a known pathogenic or likely pathogenic variant causing the condition.

If this condition is not met the test is considered investigational.

HLA-DQ Genotyping Analysis for Celiac Disease

HLA-DQ2 and HLA-DQ8 variant analysis (81370, 81375, 81376, 81377, 81382, 81383) to rule out celiac disease is considered medically necessary when ONE of the following is met

HLA-DQ indications: Equivocal small-bowel histological finding in seronegative patients; OR the member/enrollee is on a gluten-free diet and had no testing for celiac disease before initiating the diet; OR discrepant celiac-specific serology and histology; OR suspicion of refractory celiac disease where the original diagnosis remains in question.

All other indications are investigational.

HFE Sequencing and/or Deletion/Duplication Analysis for Hereditary Hemochromatosis

HFE sequencing and/or deletion/duplication analysis (81256, 81479) to establish a diagnosis of hereditary hemochromatosis is considered medically necessary when ANY of the following are met

HFE testing indications: Abnormal serum iron indices, especially elevated transferrin-iron saturation and/or elevated serum ferritin concentration indicating iron overload.

Family history criterion: First-degree relative with a diagnosis of hereditary hemochromatosis, especially if the relative has Type I HH with two C282Y mutations (homozygous).

MCM6 Targeted Variant Analysis for Lactase Insufficiency

MCM6 variant analysis (81479) for prediction of lactase insufficiency

MCM6 testing stance: MCM6 variant analysis for prediction of lactase insufficiency is considered investigational.

Not covered for prediction of lactase insufficiency.

HFE Sequencing Medical Necessity

HFE sequencing and/or deletion/duplication analysis (81256, 81479) is considered medically necessary when ANY of the following are met:

HFE criteria: A. Member has abnormal serum iron indices, especially elevated transferrin-iron saturation and/or elevated serum ferritin concentration indicating iron overload.

Supported by ACG guidance suggesting genotyping if TS >=45% and/or elevated ferritin.

Family history criterion: B. Member has a first-degree relative with a diagnosis of hereditary hemochromatosis, especially if the relative is Type I HH with two C282Y mutations (homozygous).

MCM6 / Lactase insufficiency

MCM6 (lactase persistence) targeted variant analysis (81479) coverage stance:

MCM6 status: MCM6 variant analysis for prediction of lactase insufficiency is considered investigational.

Limited sensitivity; testing may not detect all relevant single nucleotide polymorphisms.

Hereditary pancreatitis panel medical necessity

Hereditary pancreatitis multigene panel analysis (81222, 81223, 81404, 81405, 81479) is considered medically necessary when ALL of the following are met:

Pancreatitis panels initial criteria

Pancreatitis qualifying features: 1) Unexplained acute pancreatitis in childhood (<=18 years), OR 2) Recurrent (>=2) separate documented acute attacks of pancreatitis with no explanation, OR 3) Chronic pancreatitis of unknown cause, particularly onset before age 35 without heavy alcohol use.

Panel gene content: Panel should include at minimum PRSS1, SPINK1, CFTR, and CTRC.

ACG and other society guidance recommend these genes as minimum.

Hereditary IBD/Crohn's multigene panel medical necessity

Genetic testing for inflammatory bowel disease (including Crohn's) via multigene panel (81479) is considered medically necessary when ANY of the following distinct pediatric/early-onset criteria are met:

Very early onset: A. Very early onset of typical IBD symptoms before age 2 years.

Aggressive pediatric presentation: B. Member under age 18 with aggressive, refractory, or unusual IBD presentation (features include recurrent severe or atypical infections, hemophagocytic lymphohistiocytosis, autoimmune features, non‑response to multiple IBD medications, unusual disease evolution, etc.).

Family history plus symptoms: C. Member under age 18 with IBD symptoms and a family history of IBD or immunodeficiency.

Panel gene content requirement: Panel must include at minimum PRSS1, SPINK1, CFTR, and CTRC.

IBD algorithmic tests - investigational

Inflammatory bowel disease/Crohn's diagnostic and prognostic algorithmic tests are considered investigational:

Diagnostic algorithmic tests: IBD diagnostic algorithmic tests (codes including 81479, 82397, 83520, 86140, 88342, 88346, 88350) are investigational due to insufficient evidence of clinical utility.

Evidence review highlights lack of prospective utility and heterogeneity of studies (eg, Prometheus).

Prognostic algorithmic tests: IBD prognostic algorithmic tests (codes including 0203U, 81401, 83516, 83520, 86671, 88346, 88350) are investigational; PredictSURE IBD currently lacks sufficient evidence to support coverage.

Ongoing trials may provide future evidence, but current status is insufficient.

Prognostic Algorithmic IBD Tests (e.g., PredictSURE IBD)

Coverage stance based on available evidence:

Coverage determination: Prognostic serological/algorithmic tests for Crohn's disease (eg, PredictSURE IBD) are considered not supported for health plan coverage at this time due to insufficient evidence that they lead to improved health outcomes compared with current standard of care.

Supported by ECCO 2021 review and lack of published evidence demonstrating clinical utility.

Hereditary/Monogenic IBD Panel Testing

When testing may be considered medically necessary:

Indications for monogenic IBD testing: Testing for monogenic IBD should be considered when one or more clinical red flags are present, including very early age of onset (eg, <6 years, particularly <2 years), family history of IBD or immunodeficiency, consanguinity, recurrent or atypical severe infections, autoimmune features, very severe or therapy-refractory IBD, signs of hemophagocytic lymphohistiocytosis, skin/nail/hair lesions, malignancy, or multiple intestinal atresias.

Guidance based on UpToDate, ESPGHAN, and BSG summaries.

Implications: If a monogenic disorder is identified that is known to respond to specific therapies (eg, certain hematopoietic cell defects responsive to stem cell transplantation), management may change accordingly; specialist consultation is recommended.

Any use of the specific genetic tests described in this policy outside the enumerated medically necessary indications is considered investigational and excluded from coverage. Examples include targeted mutation analysis (CPT 81403), HLA‑DQ genotyping (CPTs 81370, 81375, 81376, 81377, 81382, 81383), HFE sequencing/deletion‑duplication (CPTs 81256, 81479), and MCM6 variant analysis (CPT 81479) when they are not being ordered for the specific indications listed as medically necessary in this policy.

HFE sequencing and/or deletion/duplication analysis (CPTs 81256 and 81479) performed to screen the general population is considered investigational and not covered. HFE testing is only considered medically necessary when the member meets the policy’s specific criteria (for example, documented biochemical iron overload or an appropriate first‑degree family history of Type I hereditary hemochromatosis).

The following specific gastroenterologic algorithmic tests are considered investigational (not covered): ASH FibroSURE (CPT 0002M), NASH FibroSURE (CPT 0003M), and EsoGuard (HCPCS/Proprietary code 0114U).

Prognostic serological and algorithmic tests intended to predict inflammatory bowel disease course (for example, Crohn’s prognostic algorithmic tests) are excluded from coverage due to insufficient evidence that use of these tests leads to improved health outcomes compared with standard care.

MCM6 targeted variant analysis (CPT 81479) for prediction of lactase insufficiency is considered investigational (not medically necessary) and is not covered.

MCM6 variant analysis for lactase insufficiency and inflammatory bowel disease diagnostic or prognostic algorithmic tests (including proprietary panels and serologic/algorithmic assays such as Prometheus IBD sgi Diagnostic and PredictSURE IBD) are considered investigational/not covered because current peer‑reviewed evidence does not demonstrate consistent clinical utility or improved outcomes when these tests are used to guide care.

Crohn’s prognostic algorithmic tests (for example, PredictSURE IBD) are considered not medically necessary for coverage at this time due to insufficient peer‑reviewed evidence demonstrating that their results improve patient outcomes compared with current standard management.

Coding and Billing Guidance

Known Familial Variant AnalysisCPTCovered

81403

Targeted mutation analysis for a known familial variant

HLA-DQ GenotypingCPTCovered

81370	HLA-DQ genotyping
81375	HLA-DQ genotyping
81376	HLA-DQ genotyping
81377	HLA-DQ genotyping
81382	HLA-DQ genotyping
81383	HLA-DQ genotyping

HFE Sequencing and/or Deletion/Duplication AnalysisCPTCovered

81256	HFE sequencing
81479	Unlisted molecular pathology procedure (used here for sequencing/deletion-duplication analysis)

MCM6 Targeted Variant AnalysisCPTNot Covered

81479

Used for MCM6 targeted variant analysis in this document

Other referenced test CPT/HCPCSmixed

0203U	PredictSURE IBD (prognostic algorithmic test) referenced
0114U	EsoGuard (Lucid Diagnostics) referenced
0003M	NASH FibroSURE (LabCorp) referenced

Hereditary Pancreatitis Multigene Panel CodesCPT

81222	Hereditary pancreatitis testing (gene-specific)
81223	Hereditary pancreatitis testing (gene-specific)
81404	Targeted gene panel
81405	Targeted gene panel

HFE sequencing / relatedCPTCovered

81256	HFE sequencing
81479	Unlisted molecular pathology procedure (used in document for multiple algorithmic/genetic tests)

Hereditary pancreatitis / multigene panelsCPTCovered

81222	Hereditary pancreatitis panel (single gene?)
81223	Hereditary pancreatitis panel (multi-gene?)
81404	CPT code listed for multigene panel
81405	CPT code listed for multigene panel

IBD diagnostic/prognostic algorithmic tests and related codesmixedNot Covered

81479	Unlisted molecular pathology procedure (used for IBD algorithmic tests)
82397	Prometheus/serologic assay code referenced
83520	Prometheus/serologic assay code referenced
86140	Prometheus/serologic assay code referenced
88342	Pathology code referenced
88346	Pathology code referenced
88350	Pathology code referenced
0203U	Proprietary algorithmic IBD diagnostic/prognostic test code (eg, PredictSURE/Prometheus)
81401	Molecular multianalyte algorithmic analysis
83516	Serologic assay code referenced

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Specific gastroenterologic algorithmic tests considered investigationalCPT/HCPCSNot Covered

0002M	ASH FibroSURE
0003M	NASH FibroSURE
0114U	EsoGuard

Transferrin saturation (TS) — threshold guidance

Transferrin saturation (TS) thresholdACG suggests HFE genotyping if TS ≥ 45% (and/or elevated serum ferritin)

Use before genotypingConsider standard biochemical screening (transferrin saturation, serum ferritin) prior to HFE genotyping

Context of thresholdTS ≥45% is more sensitive but may identify heterozygotes not at risk for clinical disease (per GeneReviews)

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required per payer processes for the listed genetic tests; requests must include supporting clinical documentation that the member meets medical necessity criteria described in this policy. Provide relevant clinical notes, laboratory results, family history, and indication-specific findings when submitting authorization requests.

Include laboratory values (eg, transferrin-iron saturation, serum ferritin) when applicable.
Document close relative and the known pathogenic or likely pathogenic familial variant for targeted familial variant testing requests.
For HLA-DQ testing, document clinical scenario (eg, equivocal histology, prior gluten-free diet without prior testing, discrepant serology and histology).

Denial Risk

Known Familial Variant — Investigational for Other Indications

Targeted mutation analysis for a known familial variant (81403) is considered investigational for indications other than when a close relative has a known pathogenic or likely pathogenic variant causing the condition. Requests for 81403 for other indications may be denied.

Background and Rationale

Genetic testing can confirm diagnoses of certain gastroenterologic disorders and may influence clinical management or obviate additional diagnostic testing. Covered testing in this policy includes targeted familial variant analysis, HLA‑DQ genotyping for select celiac disease scenarios, HFE gene testing for hereditary hemochromatosis when criteria are met, and specified multigene panels when clinical criteria are satisfied. Tests lacking sufficient evidence of clinical utility (for example, MCM6 testing for lactase insufficiency or certain algorithmic IBD assays) are considered investigational and are not supported for coverage.

Definitions and Key Terms

Targeted mutation analysis for a known familial variant — definition (CPT 81403)

DefinitionTargeted mutation analysis (CPT 81403) that tests for a specific pathogenic or likely pathogenic variant previously identified in a close relative.

Coverage stanceMedically necessary when the member has a close relative with a known pathogenic or likely pathogenic variant causing the condition; investigational for other indications.

Required documentationRequest should identify the close relative and the known familial pathogenic or likely pathogenic variant.

HLA-DQ2/HLA-DQ8 variant analysis — definition and CPTs

DefinitionHLA-DQ2 and HLA-DQ8 variant analysis (CPTs 81370, 81375, 81376, 81377, 81382, 81383) used to support exclusion or evaluation of celiac disease in specific clinical scenarios.

Medically necessary indications

OpenPayer

Genetic Testing: Gastroenterologic (Non‑Cancer) Disorders — Coverage Criteria

Coverage Criteria for Genetic Testing in Gastroenterology

Coding and Billing Guidance

Provider Requirements, Prior Authorization, and Documentation

Background and Rationale

Definitions and Key Terms