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CurrentWellCarePolicy N/A

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

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Defines medical necessity and investigational indications for genetic and genomic testing used to diagnose or rule out common non-cancerous gastrointestinal disorders for WellCare members and affiliated Centene health plans.

Policy Summary

PayerWellCare

PolicyGenetic Testing: Gastroenterologic Disorders (Non‑Cancerous) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Last ReviewMar 1, 2023

Next Review DateMar 1, 2023

Key ActionObtain and document relevant prior tests (eg, serum iron indices or family variant status) and complete prior authorization when billing multigene panels to verify the member meets clinical criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

V2.2023policy version

3/1/2023last review

81403; 81256; 81479example CPTs

pediatric/early-onsetIBD panel criteria

MCM6, algorithmic IBDinvestigational tests

Coverage Criteria for Genetic Testing — Gastroenterology

Known Familial Variant Analysis

Targeted mutation analysis for a known familial variant (81403) is medically necessary when:

Known familial variant analysis: The member/enrollee has a close relative with a known pathogenic or likely pathogenic variant causing the condition.

If not met, testing is investigational.

HLA-DQ Genotyping Analysis

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

HLA-DQ genotyping indications

Equivocal histology in seronegative patients: The member/enrollee has equivocal small-bowel histological finding in seronegative patients.

Policy Summary

PayerWellCare

PolicyGenetic Testing: Gastroenterologic Disorders (Non‑Cancerous) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Last ReviewMar 1, 2023

Next Review DateMar 1, 2023

SourceLink

On This Page

On gluten-free diet without prior testing: The member/enrollee is on a gluten-free diet and no testing for celiac disease was done before the diet.

Discrepant serology and histology: The member/enrollee has discrepant celiac-specific serology and histology.

Suspicion of refractory celiac disease: Patients with suspicion of refractory celiac disease where the original diagnosis remains in question.

HLA-DQ genotyping investigational: HLA-DQ2/DQ8 analysis is investigational for all other indications.

Investigational if none of the above indications are met.

HFE Sequencing and Deletion/Duplication Analysis

HFE sequencing and/or deletion/duplication analysis (81256, 81479) to establish a diagnosis of hereditary hemochromatosis is medically necessary when:

HFE sequencing indications

Abnormal iron indices: The member/enrollee has abnormal serum iron indices, especially elevated transferrin-iron saturation and/or elevated serum ferritin concentration indicating iron overload.
ACG guidance indicates consideration of HFE genotyping when transferrin saturation (TS) >= 45% and/or ferritin is elevated.
Affected first-degree relative: The member/enrollee has a first-degree relative with a diagnosis of hereditary hemochromatosis, especially if the relative is homozygous for C282Y (Type I HH).

HFE investigational uses: HFE sequencing/deletion-duplication analysis is investigational for population screening and for other unspecified indications.

Investigational for general population screening.

HFE testing - Medically Necessary

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

HFE testing criteria: A. Member has abnormal serum iron indices (elevated transferrin-iron saturation and/or elevated serum ferritin) indicating iron overload.

Supported by ACG guidance to consider HFE genotyping when TS >= 45% and/or elevated ferritin.

HFE testing criteria: 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).

Family screening of first-degree relatives is recommended by ACG.

HFE testing - Investigational

HFE sequencing and/or deletion/duplication analysis (81256, 81479) is considered investigational when ANY of the following applies:

HFE investigational: Used to screen the general population.

Explicitly investigational for population screening.

HFE investigational: Used to establish a diagnosis for indications other than those listed as medically necessary.

Policy states investigational for all other indications.

Hereditary pancreatitis panel - Medically Necessary

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

Pancreatitis core requirements

Pancreatitis B options: 1. Unexplained episode of acute pancreatitis in childhood (<=18 years); OR 2. Recurrent (>=2) documented acute pancreatitis with no explanation; OR 3. Chronic pancreatitis of unknown cause, particularly with onset before age 35 without heavy alcohol use; OR 4. History of at least one close relative with recurrent acute pancreatitis, chronic pancreatitis of unknown cause, or childhood pancreatitis of unknown cause

Panel content requirement: C. The panel includes, at a minimum, the following genes: PRSS1, SPINK, CFTR and CTRC.

Panel must include these genes to meet criteria.

Hereditary pancreatitis panel - Investigational

Hereditary pancreatitis multigene panel analysis is considered investigational for all other indications not meeting the above criteria.

Pancreatitis investigational: Any indication not meeting the specific medical necessity criteria.

Explicit investigational statement in policy.

MCM6 testing - Investigational

MCM6 targeted variant analysis (81479) for prediction of lactase insufficiency is considered investigational.

MCM6 investigational: MCM6 variant analysis for prediction of lactase insufficiency.

Policy labels this test investigational despite some literature suggesting association with lactose intolerance.

IBD multigene panel - Medically Necessary

Genetic testing for IBD (including Crohn's) via multigene panel (81479) is considered medically necessary when ANY of the following are met:

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

IBD panel criteria: Member under age 18 with aggressive, refractory, or unusual IBD presentation.

Aggressive/refractory/unusual presentations are defined in policy (see definitions).

IBD panel criteria: Member under age 18 with IBD symptoms and family history of IBD or immunodeficiency.

IBD multigene panel - Investigational

Genetic testing for IBD via multigene panel is considered investigational for all other indications.

IBD investigational: Any indication not meeting the specified pediatric/early-onset or family history criteria.

Algorithmic IBD tests - Investigational

Inflammatory bowel disease diagnostic and prognostic algorithmic tests are considered investigational.

Algorithmic tests investigational: Diagnostic algorithmic tests (listed CPT codes) and prognostic algorithmic tests (listed codes including 0203U, 81401, etc.) for IBD are investigational.

Policy explicitly lists these as investigational.

Clinical indications for targeted genetic testing

Covered when ALL of the following are met for specific test categories as supported by cited guidance:

Hereditary pancreatitis gene testing: Genetic testing is appropriate for patients with clinical evidence of pancreatitis-associated disorder or possible chronic pancreatitis with unclear etiology, especially younger patients; at minimum, testing should include PRSS1, SPINK1, CFTR, and CTRC.age younger than 30 or idiopathic CP

ACG and APA guidance cited

Monogenic IBD testing triggers: Consider genetic testing when features suggest monogenic IBD such as very early onset (especially <6 years, particularly <2 years), family history suggesting monogenic disorder or consanguinity, recurrent infections, severe refractory disease, extraintestinal autoimmune findings, or malignancy.onset typically before 6 years or presence of listed red flags

UpToDate, ESPGHAN, BSG references

Algorithmic IBD diagnostic/prognostic tests - insufficient evidence

Not covered / not supported when evidence is insufficient:

Prometheus IBD sgi Diagnostic and similar diagnostic panels: Panel-based algorithmic serologic diagnostic tests lack sufficient peer-reviewed evidence of clinical validity and utility to demonstrate improved health outcomes compared to standard of care; current evidence is insufficient to support coverage.insufficient prospective clinical utility evidence

Concert Genetics evidence review

PredictSURE IBD and other prognostic algorithmic tests: Available evidence is insufficient to support coverage for prognostic algorithmic IBD testing; ongoing trials may provide future utility but currently evidence does not support health plan coverage.insufficient evidence

Concert Genetics and ECCO workshop summary

HFE sequencing and/or deletion/duplication analysis (CPTs 81256, 81479) to screen the general population for hereditary hemochromatosis is explicitly designated investigational. The policy requires abnormal serum iron indices (e.g., elevated transferrin-iron saturation and/or elevated ferritin) or a first-degree relative with diagnosed hereditary hemochromatosis (particularly a Type I HH relative homozygous for C282Y) for testing to be considered medically necessary; absent those indications, population screening is not covered.

HLA-DQ2/DQ8 genotyping (CPT series 8137x) is covered only for the specific clinical scenarios listed (equivocal small-bowel histology in seronegative patients; patient on a gluten-free diet without prior testing; discrepant celiac serology and histology; or suspicion of refractory celiac disease). MCM6 targeted variant analysis (reported with 81479) for prediction of lactase insufficiency is considered investigational. Algorithmic IBD tests — both multigene panels for monogenic/very early-onset IBD (covered only under the pediatric/very early-onset/family-history criteria) and proprietary algorithmic diagnostic or prognostic assays — are subject to distinct positions: pediatric/very early-onset or aggressive pediatric IBD may meet medical necessity for multigene panels, whereas algorithmic diagnostic/prognostic assays are investigational except where panels meet the specified indications.

Proprietary and algorithmic inflammatory bowel disease diagnostic and prognostic tests (examples include Prometheus IBD sgi Diagnostic and PredictSURE IBD, reported with codes such as 0203U, 81401, or other panel/serologic CPTs) are designated investigational. Concert Genetics and guideline reviews cited in the policy conclude there is insufficient peer-reviewed evidence of prospective clinical utility or improved health outcomes to support coverage for these algorithmic tests.

Several test categories are explicitly investigational when used outside the policy's specified indications. Examples include targeted familial-variant analysis (81403) when no close relative has a known pathogenic/likely pathogenic variant; HLA-DQ genotyping (8137x) outside the listed celiac-related scenarios; HFE sequencing/deletion-duplication (81256, 81479) for general population screening or other unspecified uses; MCM6 targeted variant analysis (81479) for lactase prediction; and algorithmic IBD diagnostic or prognostic assays. Use outside the defined indications may be denied as investigational.

Use of the tests listed in this policy outside the defined medical-necessity criteria — including using HFE sequencing for population screening, MCM6 variant analysis for routine lactase testing, and algorithmic IBD diagnostic or prognostic assays (and other named investigational tests such as ASH FibroSURE, NASH FibroSURE, EsoGuard) — is considered not covered / investigational and may be denied.

Prometheus IBD sgi Diagnostic and similar serologic/algorithmic diagnostic panels, and prognostic tests such as PredictSURE IBD, are judged to have insufficient evidence of prospective clinical utility. The policy cites evidence reviews concluding current peer‑reviewed data do not demonstrate improved health outcomes compared with standard of care; therefore these tests are considered not medically necessary for routine coverage.

Coding and Test Codes

Known Familial Variant - Covered CPT CodesCPTCovered

81403

Targeted mutation analysis for a known familial variant

HLA-DQ Genotyping - Covered CPT CodesCPTCovered

81370	HLA DRB1,3,4,5,DQB1 Low Resolution (example HLA-DQ genotyping)
81375	HLA-DQ related code (as listed)
81376	HLA-DQ related code (as listed)
81377	HLA-DQ related code (as listed)
81382	HLA-DQ related code (as listed)
81383	HLA-DQ related code (as listed)

HFE Sequencing / Deletion-Duplication - Covered CPT CodesCPTCovered

81256	HFE gene sequencing
81479	Unlisted molecular pathology procedure (used by some HFE tests/panels)

Multigene and Test-Specific Codes (examples) - Neutralmixed

81404	Targeted genomic sequence analysis panel (multigene panel)
81405	Targeted genomic sequence analysis panel (larger panel)
81479	Unlisted molecular pathology procedure (panel/example use)
81222	Example hereditary pancreatitis gene test code listed
81223	Example hereditary pancreatitis gene test code listed
0203U	PredictSURE IBD (proprietary code listed)
0003M	NASH FibroSURE (example test code)
0114U	EsoGuard (example test code)

HFE Sequencing / Deletion-Duplication - Covered CPT Codes (alternate listing)CPTCovered

81256	HFE sequencing
81479	Unlisted molecular pathology procedure (used here for various targeted/algorithmic tests)

Hereditary pancreatitis panel codes - Covered CPT CodesCPTCovered

81222	CFTR sequencing
81223	CFTR targeted variant analysis
81404	Hereditary pancreatitis panel - tier 1 (multi-gene)
81405	Hereditary pancreatitis panel - tier 2 (multi-gene)
81479	Unlisted molecular pathology procedure (panel variants)

Algorithmic IBD diagnostic/prognostic codes - Not CoveredmixedNot Covered

0203U	Algorithmic prognostic IBD test (proprietary)
81401	Targeted genomic sequence analysis (example algorithmic test)
83516	Laboratory test (listed with algorithmic panels)
83520	Laboratory test (listed with algorithmic panels)
86671	Serologic test (listed with algorithmic panels)
88346	Microdissection pathology (listed with algorithmic panels)
88350	Immunohistochemistry (listed with algorithmic panels)

Test-specific not covered gastroenterologic tests - Not CoveredCPTNot Covered

0002M	ASH FibroSURE
0003M	NASH FibroSURE
0114U	EsoGuard

Lactase insufficiency (MCM6) - Not CoveredCPTNot Covered

81479

MCM6 targeted variant analysis (listed under investigational)

Transferrin saturation — lab threshold guidance (HFE testing)

Transferrin saturation thresholdTransferrin-iron saturation (TS) ≥ 45% is the ACG-referenced threshold to consider HFE genotyping.

Supporting ferritin criterionHFE genotyping is also indicated when serum ferritin is elevated, in combination with TS or independently as evidence of iron overload.

GeneReviews cautionGeneReviews notes TS ≥ 45% is more sensitive but may identify heterozygotes who are not at risk of clinical disease.

Provider Actions, Documentation & Authorization

Note

Reference CPTs, labs & coding guidance before claim submission

Reference the policy reference table and coding guidance in this document before submitting claims; the table lists common CPT mappings and laboratories for the tests addressed and providers should verify current coding prior to claim submission.

Prior Authorization

Prior authorization required for hereditary pancreatitis and IBD multigene panels

Obtain prior authorization when billing hereditary pancreatitis multigene panels or IBD multigene panels to confirm the member meets the policy's specified clinical criteria (age/onset, recurrence/unexplained disease, or family history) before testing is performed.

Hereditary pancreatitis panel codes cited: 81222, 81223, 81404, 81405, 81479
IBD multigene panel code cited: 81479

Prior Authorization

Prior authorization/review may be required for algorithmic IBD tests

Algorithmic IBD diagnostic and prognostic tests (including Prometheus IBD sgi Diagnostic and PredictSURE IBD) lack sufficient evidence and therefore may require prior authorization or review and can be denied based on insufficient evidence of clinical utility.

Algorithmic diagnostic/prognostic tests are listed as investigational and not supported for coverage
Documentation of clinical necessity and rationale may be requested during authorization

Step Therapy

Obtain serum iron indices (TS and ferritin) before HFE genetic testing

Before ordering HFE sequencing (81256) or panel testing (81479), document initial laboratory evaluation with serum iron indices — transferrin-iron saturation and ferritin — since abnormal results (eg, TS ≥45% and/or elevated ferritin per ACG guidance) are the policy triggers for genetic testing.

ACG guidance indicates HFE genotyping if transferrin saturation (TS) ≥ 45% and/or serum ferritin is elevated

Step Therapy

Stepwise/targeted gene testing recommended before broader panels

Follow guideline-recommended stepwise testing for hereditary pancreatitis/chronic pancreatitis: perform targeted testing of core genes (at minimum PRSS1, SPINK1, CFTR, CTRC) before considering broader panels.

Policy requires panels include PRSS1, SPINK1, CFTR, and CTRC at minimum

Documentation Required

Document known familial pathogenic/likely pathogenic variant for targeted testing (81403)

When ordering targeted familial variant testing (81403), provide documentation that a close relative has a known pathogenic or likely pathogenic variant; the policy requires this evidence to consider testing medically necessary.

Close relative with documented pathogenic or likely pathogenic variant must be identified in the record

Documentation Required

Document abnormal iron studies or qualifying family history for HFE testing

For HFE sequencing or deletion/duplication testing (81256, 81479), include clinical documentation of abnormal serum iron indices (elevated transferrin-iron saturation and/or ferritin) or a first-degree family history of Type I hereditary hemochromatosis (two C282Y mutations).

Document transferrin-iron saturation and serum ferritin values
If applicable, document family history specifying relative's genotype (eg, C282Y homozygote)

Documentation Required

Document qualifying clinical scenario when ordering HLA-DQ genotyping

When ordering HLA-DQ genotyping (81370/81375/81376/81377/81382/81383), document one of the qualifying clinical scenarios (equivocal histology in seronegative patient; patient on gluten-free diet without prior testing; discrepant serology and histology; or suspicion of refractory celiac disease).

Specify which qualifying scenario applies in the clinical record or authorization request

Documentation Required

Provide required clinical documentation that matches the policy criteria

Ensure the submitted clinical documentation supports the policy's medical necessity criteria for the requested test (for example: abnormal TS/ferritin for HFE testing; personal history plus age/onset/recurrence/family history for hereditary pancreatitis panels; age of onset and severity/family history for IBD panels).

Attach relevant lab results, clinical notes, and family history details to the prior authorization or claim
Clinical documentation must align with the specific criteria listed in the policy

Documentation Required

Include clinical justification (presentation, age of onset, family history) with the order

Include clinical justification when ordering genetic tests: document clinical presentation, age of onset, family history, and diagnostic rationale (eg, idiopathic disease, refractory/severe disease) consistent with professional guidance to support medical necessity.

For monogenic IBD suspicion, include red-flag features (very early onset, recurrent infections, consanguinity, severe/refractory disease)
For pancreatitis, include age at onset and exclusion of common causes

Denial Risk

Known familial variant testing (81403) — investigational if no documented affected relative

Targeted mutation analysis for a known familial variant (81403) is investigational and may be denied when there is no documented close relative with a pathogenic or likely pathogenic variant; do not submit without that documentation.

Policy explicitly deems 81403 investigational for indications other than documented familial variant

Denial Risk

HLA-DQ testing — investigational outside specified celiac indications

HLA-DQ genotyping (8137x series) is investigational for indications other than the listed clinical scenarios; tests ordered outside those scenarios may be denied as not medically necessary.

HLA-DQ testing is covered only for the specific celiac-related scenarios in the policy

Denial Risk

HFE sequencing/panel testing — population screening is investigational and may be denied

HFE sequencing or panel testing (81256, 81479) used for population screening is considered investigational and may be denied; do not bill these codes for general population screening.

Policy states HFE sequencing/deletion-duplication for general population screening is investigational

Billing Rule

HFE testing (81256, 81479) — billing for population screening can trigger denial

Billing HFE sequencing codes (81256 or 81479) for population screening or indications not listed as medically necessary may result in denial; ensure the indication and supporting documentation meet policy criteria before submission.

81256 and 81479 are cited as denial-triggering when used for population screening

Denial Risk

Investigational tests may be denied as not medically necessary

Tests designated investigational in the policy (for example, MCM6 variant analysis, algorithmic IBD tests, and specific listed tests) may be denied as not medically necessary; do not submit without strong supporting documentation or prior authorization approval if requested.

Examples listed as investigational/not covered include MCM6 (81479), Prometheus, PredictSURE, ASH FibroSURE (0002M), NASH FibroSURE (0003M), and EsoGuard (0114U)

Denial Risk

Insufficient evidence for algorithmic IBD tests can trigger denial

Because Prometheus IBD sgi Diagnostic and similar algorithmic IBD tests currently lack prospective clinical utility evidence, use of these tests may be denied for insufficient evidence of improved health outcomes.

Concert Genetics evidence review finds insufficient peer-reviewed evidence of clinical utility for Prometheus

Denial Risk

Prognostic IBD tests (e.g., PredictSURE IBD) — coverage risk due to insufficient evidence

Prognostic IBD tests such as PredictSURE IBD are judged to have insufficient evidence to support coverage at this time and may be denied; if ordering, expect requests for justification or prior authorization documentation.

Policy notes ongoing trials but current evidence does not support health plan coverage

Note

Order or consult specialist for suspected monogenic IBD

When evaluating suspected monogenic IBD, involve or refer to a specialist (eg, pediatric gastroenterology or immunology) for ordering and interpretation, as recommended by the policy for complex cases.

Policy advises specialist consultation/ordering for suspected monogenic IBD due to complexity and management implications

Note

Documentation Required

Ensure submitted clinical documentation directly supports the policy medical necessity criteria

Clinical documentation submitted must support the specific medical necessity criteria listed in the policy (eg, lab results, family history, age of onset, recurrence, and exclusion of other causes) and be attached to prior authorization requests or claims.

Required documentation examples: transferrin saturation and ferritin values; age at onset and recurrence details for pancreatitis; age and severity/family history for IBD panels

Member Eligibility and Test Ordering Requirements

Eligibility for testing is determined by the specific coverage criteria for each test type. Generally, targeted familial-variant testing requires a close relative with a documented pathogenic or likely pathogenic variant; HLA-DQ genotyping requires one of the specified celiac-related clinical scenarios; HFE sequencing requires abnormal iron indices or an affected first-degree relative; hereditary pancreatitis panels require personal pancreatitis plus listed age/onset/recurrence/family-history criteria; and IBD multigene panels are limited to very early-onset or pediatric aggressive/refractory/unusual presentations or pediatric cases with relevant family history.

Additional eligibility and procedural notes include the panel content requirement for hereditary pancreatitis testing — the panel must include at minimum PRSS1, SPINK1, CFTR, CTRC — and guideline-aligned age considerations (for example, genetic evaluation for pancreatitis is suggested in younger patients without an evident cause). Professional guidance cited (ACG, APA) supports targeted testing when clinical features and family history meet defined thresholds.

Monogenic IBD testing (multigene panels) is eligible primarily for infants and children with red-flag features: very early onset (particularly <2 years, and generally <6 years), family history suggestive of monogenic disease or consanguinity, recurrent severe or atypical infections, severe refractory disease, extraintestinal autoimmune features, malignancy, or other listed signs. Such presentations warrant specialist involvement (pediatric gastroenterology and immunology) and consideration of targeted genetic evaluation.

HLA-DQ genotyping eligibility is limited to the policy's four clinical scenarios for ruling out celiac disease: equivocal small-bowel histology in seronegative patients; patients already on a gluten-free diet with no prior testing; discrepant serology and histology; and suspected refractory celiac disease. Testing outside those scenarios is investigational.

HFE testing eligibility requires prior laboratory evidence or family history: genetic testing is considered medically necessary when the member has abnormal serum iron indices (notably elevated transferrin-iron saturation and/or elevated ferritin) or when a first-degree relative has a diagnosis of hereditary hemochromatosis (particularly Type I with two C282Y mutations). The ACG guidance referenced suggests considering HFE genotyping when transferrin saturation is >= 45% and/or ferritin is elevated.

Before ordering HFE sequencing, providers are expected to obtain and document serum iron indices (transferrin‑iron saturation and ferritin). Documentation supporting abnormal iron studies or the relevant positive family history is required for coverage review; failure to document these prerequisites may lead to denial.

Ordering recommendations align with professional society guidance: for hereditary pancreatitis and chronic pancreatitis of unclear etiology, initial targeted testing of key genes (PRSS1, SPINK1, CFTR, CTRC) is recommended before broader panels; for HFE testing, use serum iron indices as triggers; and testing for suspected monogenic IBD should involve or be ordered by specialists experienced in these conditions.

Tests and Uses Not Covered / Investigational

Tests used outside the policy's specified indications are designated investigational and thus not covered. This includes targeted familial-variant testing without a documented familial pathogenic variant (81403), HLA‑DQ genotyping outside the listed celiac scenarios (8137x), HFE sequencing for population screening (81256, 81479), MCM6 variant analysis for lactase prediction (81479), and algorithmic IBD diagnostic/prognostic assays and other named investigational tests (e.g., ASH FibroSURE 0002M, NASH FibroSURE 0003M, EsoGuard 0114U).

Specific tests and test categories listed as not covered or investigational include MCM6 targeted variant analysis for lactase insufficiency (reported with 81479), multiple algorithmic diagnostic and prognostic IBD tests (codes such as 81479, 82397, 0203U, 81401), and named investigational assays such as ASH FibroSURE (0002M), NASH FibroSURE (0003M), and EsoGuard (0114U).

Prometheus IBD sgi Diagnostic and PredictSURE IBD (and similar algorithmic serologic/prognostic IBD tests) are not supported for coverage because evidence reviews concluded current peer‑reviewed literature does not demonstrate sufficient prospective clinical utility or improved outcomes to justify routine health plan coverage at this time.

Background and Scope

Background: Genetic testing for non‑cancerous gastroenterologic disorders is used to confirm diagnoses that may alter clinical management or avoid further diagnostic procedures. This policy addresses testing for conditions including celiac disease (HLA‑DQ genotyping), hereditary hemochromatosis (HFE sequencing/deletion‑duplication), lactase persistence/insufficiency prediction (MCM6 variant analysis), hereditary pancreatitis (multigene panels requiring PRSS1, SPINK1, CFTR, CTRC), and inflammatory bowel disease/monogenic IBD multigene testing. Coverage is determined by condition-specific clinical criteria and pertinent guideline recommendations.

Definitions and Key Terms

Purpose of testing

Primary purposeConfirm a diagnosis in a symptomatic patient to guide management or avoid further diagnostic workup.

Application scopeUsed for non-cancerous gastroenterologic disorders (eg, celiac disease, hereditary hemochromatosis, lactase insufficiency, hereditary pancreatitis, IBD-related panels).

Impact on carePositive genetic findings can alter management decisions and the need for additional testing or interventions.

Close relatives (policy definition)

Definition — close relativesFirst-, second-, and third-degree blood relatives on the same side of the family.

First-degree examplesParents, siblings, and children.

Second- and third-degree examplesSecond-degree: grandparents, aunts/uncles, nieces/nephews, grandchildren, half-siblings. Third-degree: great grandparents, great aunts/uncles, great grandchildren, first cousins.

Aggressive, refractory, or unusual IBD presentation — examples

Core definitionAggressive, refractory, or unusual IBD presentation includes severe, atypical, or treatment‑resistant disease features warranting genetic evaluation.

Infectious/immune red flagsRecurrent severe or atypical infections consistent with primary immunodeficiency; hemophagocytic lymphohistiocytosis.

Autoimmune/malignant featuresAutoimmune presentations (eg, IPEX features), malignancies, multiple intestinal atresias, or unusual disease evolution.

Therapy non-responseNon-response to multiple IBD medications (refractory disease).

MCM6 targeted variant analysis

Test descriptionTargeted variant analysis of MCM6 (lactase persistence/lactase insufficiency-associated variant), typically reported using unlisted molecular pathology coding (eg, 81479).

Clinical intentOffered to predict lactase insufficiency (lactase non‑persistence) based on known MCM6-associated variants.

Coverage stancePolicy identifies MCM6 targeted variant analysis as investigational for prediction of lactase insufficiency.

Hereditary pancreatitis multigene panel

DefinitionMultigene panel testing designed to detect pathogenic variants in genes associated with hereditary pancreatitis.

Required genesPolicy requires panels to include at minimum PRSS1, SPINK1, CFTR, and CTRC to meet medical necessity criteria.

Typical use caseUsed for individuals with personal history of pancreatitis plus early-onset, recurrent, unexplained, chronic early-onset, or relevant family history features.

Monogenic inflammatory bowel disease (monogenic IBD)

DefinitionMonogenic IBD refers to rare, typically early-onset single-gene disorders (over 60 described) that cause IBD‑like intestinal inflammation and may require specialized management.

Clinical triggersConsider when very early onset (esp <2 years, <6 years), family history of IBD or immunodeficiency, recurrent infections, severe refractory disease, or extraintestinal autoimmune findings are present.

Management implicationsSome monogenic disorders may respond to immunology-directed therapies or hematopoietic stem cell transplantation for certain defects; specialist consultation is recommended.