ModifiedCentenePolicy N/A

Genetic Testing: Lung Disorders (AATD and Donor-Derived Cell-free DNA)

Clinical coverage criteria for genetic and molecular testing related to lung disorders, including alpha-1 antitrypsin deficiency testing and donor-derived cell-free DNA testing for lung transplant rejection, applicable to Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyGenetic Testing: Lung Disorders (AATD and dd-cfDNA)

Policy CodePolicy N/A

Change TypeMaterial revisions and new criteria added

Effective DateN/A

Next Review DateN/A

Key ActionOrder dd-cfDNA for lung transplant recipients only when test not performed in prior 12 months and specified clinical criteria are met; follow prior authorization procedures.

SourceLink

POLICY UPDATE CHANGES

In SERPINA1 Common Variant Analysis or Sequencing and/or Deletion/Duplication Analysis criteria, updated criteria to better align with current guidelines, allowing for an expansion to coverage.

New criteria created for donor-derived cell-free DNA for lung transplant rejection based on LCD guidelines.

In SERPINA1 Known Familial Variant Analysis criteria, moved criteria to policy 'Genetic Testing: General Approach to Genetic and Molecular Testing' to consolidate criteria for known familial variant tests.

Replaced wording 'coverage criteria' with 'criteria' throughout the document; titles, overview, coding, reference table, background and references updated for versioning and semi-annual review cadence.

7AATD indications listed

3dd-cfDNA coverage triggers

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

SERPINA1 Common Variant or Sequencing/Deletion-Duplication Analysis

Covered when ANY of the following are met

AATD Testing Indications: Member/enrollee has any of the following: 1) Abnormally low AAT plasma level (less than 120 mg/dL) or borderline level (90-140 mg/dL); 2) Early-onset emphysema (45 years of age or younger); 3) Emphysema in the absence of additional recognized risk factors (e.g., smoking, occupational dust exposure); 4) Emphysema with prominent basilar hyperlucency; 5) Otherwise unexplained liver disease; 6) Necrotizing panniculitis; 7) C-ANCA positive vasculitis (granulomatosis with polyangiitis); 8) Bronchiectasis without evident etiology; 9) Sibling with known AAT deficiency.

Tests: CPT 81332 (SERPINA1 common variant analysis) or CPT 81479 (sequencing and/or deletion/duplication analysis).

Evidence-Based Donor-Derived Cell-free DNA for Lung Transplant Rejection

Covered when ALL of the following are met

dd-cfDNA Evidence-Based Use: A. Member/enrollee has undergone lung transplantation; AND B. The test has not been performed in the last 12 months; AND C. Member/enrollee meets at least one of: 1) clinical signs of acute rejection; OR 2) a biopsy was performed and is inconclusive for rejection; OR 3) member/enrollee is being monitored for adequacy of immunosuppression.

Test example CPT 81479; default monitoring frequency once every 12 months. Intended use documentation should indicate whether the test is to assess adequacy of immunosuppression, further evaluate allograft status, serve as a rule-out for acute rejection, or assess inconclusive biopsy results.

Emerging Evidence Donor-Derived Cell-free DNA

Emerging dd-cfDNA Tests: Donor-derived cell-free DNA tests that lack sufficient evidence of clinical validity (for example tests reported with code 0118U) are considered investigational for management of patients after lung transplantation.

Coverage not supported for tests lacking established clinical validity or utility.

Other Covered Lung Disorders

Covered when ALL of the following are met

Other Genetic Lung Disorders: Genetic testing to establish or confirm the diagnosis of selected rare genetic lung disorders (examples include familial pulmonary fibrosis; primary ciliary dyskinesia; pulmonary lymphangioleiomyomatosis; pulmonary alveolar proteinosis) is medically necessary when the member/enrollee demonstrates clinical features consistent with the disorder.

Clinical features for specific disorders are referenced to resources such as GeneReviews, OMIM, and Genetics Home Reference.

Revised and New Criteria Sets

Document indicates creation of NEW criteria sets and revisions for specific test categories (SERPINA1 analyses; donor-derived cfDNA for lung transplant rejection).

SERPINA1 criteria revision: SERPINA1 Common Variant Analysis or Sequencing and/or Deletion/Duplication Analysis criteria were updated to better align with current guideline recommendations and to expand coverage; Known Familial Variant Analysis criteria were moved to the General Approach to Genetic and Molecular Testing policy.

Full eligibility logic and associated operational details are provided elsewhere in the policy excerpt.

Donor-derived cfDNA criteria added: A new, evidence-based criteria set for donor-derived cell-free DNA testing to assess lung transplant rejection was created based on MolDX LCD L38582 guidance.

Full eligibility logic and prior authorization or plan-specific requirements follow Health Plan and LCD/NCD procedures.

SERPINA1 (alpha-1 antitrypsin) genetic testing using CPT 81332 (common variant analysis) or CPT 81479 (sequencing and/or deletion/duplication analysis) is considered investigational for any indication not explicitly listed in the policy criteria. The policy enumerates specific clinical and laboratory features that support medical necessity for AATD testing; uses outside those listed (i.e., all other indications) do not meet the evidence threshold and are investigational.

The excerpt does not provide an explicit list of individual tests or commercial platforms that are categorically excluded. Providers should refer to Health Plan administrative policies and the Concert Platform for up-to-date listings of registered tests and any plan-specific exclusions.

Use of SERPINA1 common variant analysis or full gene sequencing/deletion-duplication analysis for purposes other than those enumerated (for example, broad population screening or diagnostic uses not supported by the listed clinical or laboratory triggers) is considered investigational. The policy’s background and rationale reference guideline-based triggers (e.g., abnormal AAT plasma levels, early-onset emphysema, unexplained liver disease) as the appropriate indications for testing.

Within the provided excerpt there are no explicit statements formatted as numeric 'not medically necessary' listings. The document emphasizes that coverage decisions depend on the policy criteria and plan terms, and that indications not meeting the enumerated criteria are investigational.

Covered Indications

Diagnostic testing for AATD when listed clinical/lab features present; dd-cfDNA for lung transplant recipients meeting post-transplant criteria; testing to establish/confirm rare genetic lung disorders when clinical features present

Diagnostic and Post-Transplant Testing: Diagnostic testing for alpha-1 antitrypsin deficiency (AATD) when listed clinical or laboratory features are present; donor-derived cell-free DNA testing for lung transplant recipients who meet post-transplant criteria; and genetic testing to establish or confirm selected rare genetic lung disorders when clinical features are present.

Refer to individual criteria sets for detailed eligibility requirements and applicable CPT codes (e.g., 81332, 81479).

Donor-derived cell-free DNA testing for lung transplant rejection — new criteria set aligned with MolDX LCD L38582

Donor-derived cfDNA for Lung Transplant Rejection (MolDX-aligned): A. Member/enrollee is a lung transplant recipient; AND B. The peripheral blood dd-cfDNA test has not been performed within the prior 12 months; AND C. Intended use aligns with one or more of: evaluation of adequacy of immunosuppression, further evaluation of allograft status when there is physician-assessed pretest probability of rejection, rule-out of acute rejection to inform biopsy decisions in validated populations, or assessment when biopsy is inconclusive.

Coding

SERPINA1 Common Variant AnalysisCPTCovered

81332

SERPINA1 common variant analysis

Sequencing and/or Deletion/Duplication Analysis; Evidence-based dd-cfDNACPTCovered

81479

Unlisted molecular pathology procedure (used here for sequencing and/or deletion/duplication and some dd-cfDNA tests)

Emerging Evidence dd-cfDNACPTExperimental

0118U

Emerging dd-cfDNA test (specific proprietary code)

Common ICD Codes for Transplant MonitoringICD-10

T86.810	Complications of transplanted lung
Z48.24	Encounter for aftercare following lung transplant

AAT plasma level threshold

AAT plasma level interpreted as abnormalLess than 120 mg/dL

AAT plasma level considered borderline90-140 mg/dL

Normal range referenced in guidelineReported normal range ~83-200/220 mg/dL (source guideline reporting variability)

dd-cfDNA repeat interval

Minimum interval before repeating dd-cfDNA for monitoringNot performed in the last 12 months (default monitoring frequency once every 12 months)

Coverage condition regarding prior test timing

Provider Actions & Requirements

Prior Authorization

Prior Authorization & Frequency for dd-cfDNA

Prior authorization may be required for donor-derived cell-free DNA (dd-cfDNA) testing (CPT 81479) when used for post-transplant monitoring. When prior authorization is required, the test is generally considered medically necessary only if performed no more frequently than once every 12 months for routine surveillance absent guideline-specified alternative intervals. More frequent testing may be considered when clinically justified (for example, new or worsening signs/symptoms of rejection, inconclusive biopsy results, or to assess adequacy of immunosuppression) but may still require prior authorization and documentation of clinical rationale.

Affected code: CPT 81479
Default surveillance interval: once every 12 months
Exceptions: symptomatic evaluation, inconclusive biopsy, assessment of immunosuppression adequacy

Billing Rule

Not Covered / Investigational

Donor-derived cell-free DNA assays that lack demonstrated clinical validity and utility (for example, tests identified as having insufficient evidence) are classified as investigational and are not covered for management of lung transplant recipients. The policy specifically calls out such emerging/proprietary assays as not meeting coverage thresholds when evidence of validity is lacking.

The excerpt does not include a named, comprehensive list of not-covered genetic tests or platforms. For determinations about specific assays, providers should consult the Health Plan’s coverage document updates and the Concert Platform for registered test status and plan-specific exclusions.

Eligibility Requirements

Eligibility requirements for SERPINA1 testing and dd-cfDNA testing are defined by the policy criteria themselves (see covered indications). This block is reserved for detailed eligibility logic (e.g., required clinical findings, laboratory thresholds, timing relative to transplantation) which are captured in the criteria sections of the policy.

Additional eligibility requirements for dd-cfDNA include timing and intended use documentation: the test must not have been performed within the prior 12 months for routine monitoring unless otherwise clinically justified, and the intended use should align with evaluating immunosuppression adequacy, assessing allograft status, or informing biopsy decisions.

Background

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder leading to low or dysfunctional AAT protein with associated lung and liver disease. The policy references guideline-based clinical triggers for diagnostic evaluation: an abnormally low plasma AAT level (less than 120 mg/dL) or borderline levels (90–140 mg/dL), early-onset emphysema (≤45 years), emphysema without typical risk factors, basilar-predominant emphysema, unexplained liver disease, necrotizing panniculitis, C-ANCA–positive vasculitis, bronchiectasis of unclear cause, and a sibling with known AAT deficiency. Genetic testing is used to establish diagnosis and identify affected family members.

Definitions

AATD — definition and clinical implications

DefinitionAlpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disorder causing decreased production or dysfunctional alpha-1 antitrypsin (AAT) protein leading to increased risk of lung and liver disease.

Clinical implications - pulmonaryIncreased risk of early-onset emphysema (≤45 years), emphysema without typical risk factors, basilar-predominant hyperlucency, and bronchiectasis without evident etiology.

Clinical implications - extrapulmonaryAssociated with unexplained liver disease and necrotizing panniculitis; family members may be at risk and warrant testing.

dd-cfDNA — definition and intended use

DefinitionDonor-derived cell-free DNA (dd-cfDNA) is a peripheral blood measurement of donor DNA fragments used as a minimally invasive biomarker to assess allograft injury or rejection after transplantation.