Verify CPT and registered test on Concert Genetics

Use the CPT/PLA code that corresponds to the exact test performed and confirm the laboratory test listing on the Concert Genetics platform before submitting claims.

• Examples of referenced CPT codes include 81403, 81405, 81408, 81410, 81411, 81479.
• If a panel is performed, the appropriate panel code must be used and providers should confirm registered tests on the Concert Genetics platform.

Prior authorization requires clinical criteria documentation

Genetic sequencing and multigene panel tests listed in this policy require documentation that the member meets the policy's clinical criteria for the requested test to be considered medically necessary.

• Covered/referenced CPT/PLA codes include 81400–81411 and 81479 as applicable.
• Provide clinical evidence as specified for the disorder (e.g., aortic Z-score, systemic score, major/minor criteria).

Choose phenotype-consistent multigene panel with required genes

Order a multigene panel when the member's phenotype is consistent with HTAD or other listed syndromes and ensure the panel includes the relevant genes named in the policy.

• HTAD panels should include, at minimum, genes such as ACTA2, FBN1, MYH11, TGFBR1, and TGFBR2 (GeneReviews lists additional HTAD genes).
• Select a panel that matches the clinical phenotype to limit irrelevant findings.

Confirm and adhere to plan-level prior authorization processes

Follow the Health Plan's administrative policies — prior authorization may be required per the plan's processes and coverage decisions are subject to plan terms and procedures.

• Confirm any plan-level prior authorization requirements before ordering.
• Coverage is subject to terms, conditions, exclusions, and limitations of the member's coverage documents.

Clinical-first ordering for FBN1 sequencing/CNV testing

Use a clinical-first approach for FBN1 testing: perform clinical evaluation and apply diagnostic scoring (aortic Z-score and systemic features) and order FBN1 sequencing and/or deletion/duplication (81408, 81479) when clinical features suggest Marfan but do not meet definitive criteria.

• Indication requires aortic root enlargement (Z-score ≥2) or dissection plus ectopia lentis or systemic score ≥7 as described in the policy.
• Molecular testing is appropriate in equivocal cases to clarify diagnosis.

Prefer targeted familial variant testing (81403) when family variant known

When a familial pathogenic or likely pathogenic variant has been identified in an index case, order targeted familial variant analysis (CPT 81403) for at-risk relatives as the preferred testing strategy.

• Targeted mutation analysis (81403) is covered only when a close relative has a known pathogenic or likely pathogenic variant.
• Targeted familial testing is investigational and not covered for indications without a documented familial variant.

Initial testing: targeted single-gene or panels including key EDS genes

For suspected cEDS or vEDS, begin with targeted single-gene testing (COL5A1/COL5A2 for cEDS; COL3A1 for vEDS) or panels that include these genes as the appropriate initial strategy.

• cEDS panels should be limited to COL5A1, COL5A2, and COL1A1 as specified.
• vEDS testing should include COL3A1 sequencing and/or deletion/duplication analysis.

Reflex to CNV/deletion-duplication testing after negative sequencing

If sequencing does not identify a causative variant and clinical suspicion remains, perform reflex or complementary CNV/deletion-duplication testing to detect large deletions or duplications.

• Complement sequencing with a CNV detection strategy when no variant is identified.
• Document the rationale for reflex CNV testing in the medical record.

Include documented family history for targeted familial variant requests

Provide documented family history showing a close relative with a known pathogenic or likely pathogenic variant when requesting targeted familial mutation analysis (81403).

• Close relative definition includes first-, second-, and third-degree blood relatives per policy notes.
• Lack of documented familial variant will render targeted testing investigational/not covered.

Attach clinical evidence (aortic Z-score, systemic score, disorder-specific features)

Include clinical documentation demonstrating diagnostic features required by the policy (e.g., aortic root Z-score, systemic feature scoring for Marfan) when ordering molecular testing.

• For Marfan, document aortic root enlargement (Z-score ≥2) and either ectopia lentis or systemic score ≥7 with listed features.
• For LDS, TAAD, cEDS, and vEDS, provide the specific clinical features listed in the policy that support medical necessity.

Document family history, aortic measurements, and key clinical findings

Ensure the medical record includes family history, aortic measurements (Z-score), and presence of key clinical features (ectopia lentis, systemic score, arterial events) to support the molecular testing request.

• Document prior imaging, measurements, and relevant physical exam findings.
• Record family history details, including degree of relative and documented diagnoses or variants.

Provide vEDS-specific clinical documentation (major/minor criteria and events)

For vEDS testing, document presence of major criteria or combinations of minor criteria and family history or clinical events (e.g., arterial rupture <40 years, unexplained sigmoid colon rupture) to justify molecular testing.

• Major criteria include family history with documented COL3A1 variant, arterial rupture <40, unexplained sigmoid colon rupture, uterine rupture in third trimester, or carotid-cavernous sinus fistula without trauma.
• If sequencing is negative but suspicion persists, document rationale for CNV testing.

Investigational: targeted familial testing without a known proband variant

Do not submit targeted familial variant analysis for relatives unless a pathogenic or likely pathogenic variant has been identified in the proband; such requests are investigational and may be denied.

• Targeted mutation analysis (81403) is covered only when a close relative has a known pathogenic or likely pathogenic variant.
• Requests without an identified familial variant are considered investigational.

Investigational: panels for isolated hypermobility/hEDS

Comprehensive multigene panels are investigational for isolated hypermobility and hypermobile Ehlers-Danlos syndrome (hEDS) and for other indications not meeting the policy's specified criteria; such requests risk denial.

• Genetic testing for isolated hEDS is not appropriate because causative genes are unknown.
• Panel requests for indications outside listed criteria may be considered investigational.

Investigational: FBN1 testing outside specified Marfan indications

FBN1 sequencing and/or deletion/duplication (81408, 81479) to establish or confirm Marfan syndrome is investigational for indications outside the policy-specified Marfan criteria and may be denied.

• Only order FBN1 testing when the member meets the clinical criteria enumerated in the policy (e.g., aortic Z-score and systemic findings).
• Requests for other indications are considered investigational.

Investigational: TAAD panel requests outside familial TAAD criteria

TAAD multigene panels are investigational for indications other than the familial TAAD criteria described in the policy and may be denied if requested outside those uses.

• Familial TAAD panels must meet criteria including aortic disease, exclusion of other disorders, compatible family history, and minimum gene content.
• Panels for other indications are considered investigational.

Investigational: cEDS and COL3A1 testing for non-listed indications

Classic EDS (cEDS) and COL3A1 (vEDS) testing are investigational for indications outside the policy-listed criteria, including isolated hypermobility/hEDS; such requests risk denial.

• cEDS panels are limited to COL5A1, COL5A2, and COL1A1 and investigational for other uses.
• vEDS testing (COL3A1) is investigational for indications outside the listed major/minor criteria.

Testing cascade requirement: proband variant must be identified for targeted relative testing

If a pathogenic variant is not identified in the index case, targeted testing of relatives may be precluded; only relatives with the identified pathogenic variant in the proband should undergo targeted testing and subsequent imaging.

• Documented identification of a proband variant is required to trigger targeted cascade testing and imaging for relatives.
• Absence of a proband variant may render targeted familial testing inappropriate.

Denial risk for tests not meeting policy or plan terms

Coverage decisions are subject to the member's plan terms and administrative policies; tests that do not meet the policy's medical necessity criteria or plan contractual limitations may be denied.

• Confirm benefits and prior authorization requirements with the member's Health Plan before testing.
• Maintain complete documentation to support medical necessity.

Document familial testing strategy; counseling not explicitly mandated

The policy emphasizes familial testing strategies and cascade testing but does not explicitly mandate pre- or post-test genetic counseling; document counseling when performed and follow guideline recommendations for cascade testing.

• Policy background supports testing an affected family member first to identify a familial pathogenic variant.
• Record whether genetic counseling was provided even though the policy does not explicitly require it.

Recommend counseling and targeted testing for first-degree relatives

When a pathogenic variant is identified in a proband, offer and document genetic counseling and targeted testing for first-degree relatives as recommended by professional guidance.

• ACC guidance recommends counseling and testing of first-degree relatives if a mutant gene is identified in a patient.
• Only relatives with the identified pathogenic variant should undergo aortic imaging.

Document implications of results and provide counseling as appropriate

Consider and document the implications of genetic test results for treatment, natural history, and recurrence risk; the policy implies genetic counseling is part of cascade testing and management.

• Use test results to guide aortic surveillance, surgical decisions, and family risk assessment.
• Document counseling about recurrence risk and management implications when testing is performed.

Order tests based on clinical evaluation and family strategy; document indications

Order testing guided by clinical evaluation and family testing strategies; ensure the ordering provider documents clinical indications and family history per the policy's requirements.

• Policy does not restrict which provider may order testing; providers must exercise professional judgment and document indications.
• Include disorder-specific clinical findings and family history in the order to support medical necessity.

Document recommendations and actions for first-degree relatives after proband variant identification

When recommending testing or counseling for first-degree relatives after identification of a pathogenic variant, the ordering provider should document the test rationale and referral/counseling actions in the medical record.

• Document that first-degree relatives were offered testing/counseling and any follow-up imaging plans.
• Ensure records identify the proband variant and degree of relatedness for cascade testing.

Ordering responsibility: professional judgment expected (no provider restriction specified)

The policy does not specify which clinicians may order tests; providers are expected to use professional medical judgment and be responsible for appropriate ordering and documentation.

• Ensure documentation supports medical necessity regardless of ordering clinician specialty.
• Follow plan prior authorization and ordering procedures as applicable.