ModifiedCentenePolicy N/A

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

Defines medical necessity criteria for genetic and molecular testing for alpha-1 antitrypsin deficiency (AATD), donor-derived cell-free DNA (dd-cfDNA) for lung transplant rejection, and other genetic lung disorders for Centene health plans.

Policy Summary

PayerCentene

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

Policy CodePolicy N/A

Change TypeCriteria added and revised (AATD expandeddd-cfDNA new)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document transplant status and that dd-cfDNA was not performed in the prior 12 months when ordering donor-derived cfDNA testing.

SourceLink

POLICY UPDATE CHANGES

In SERPINA1 common variant and sequencing/deletion-duplication criteria, updated criteria to better align with current guidelines and expanded coverage.

Moved Known Familial Variant Analysis criteria to the General Approach to Genetic and Molecular Testing policy for consolidation.

Adopted default frequency of once every 12 months for monitoring with dd-cfDNA in absence of specific guideline regimen.

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

Throughout the policy, phrasing 'coverage criteria' was replaced with 'criteria' for consistency.

2major test categories covered

>=1AATD CPTs called out

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Coverage Criteria

SERPINA1 Common Variant Analysis or Sequencing and/or Deletion/Duplication Analysis (AATD)

Covered when ANY of the following are present:

AATD diagnostic indications: Member has any of: 1) Abnormally low (<120 mg/dL) or borderline (90-140 mg/dL) AAT plasma level; 2) Early-onset emphysema (<=45 years); 3) Emphysema in the absence of additional 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.

Evidence-Based dd-cfDNA for Lung Transplant Rejection

Covered when ALL of the following are met:

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

Emerging/Investigational dd-cfDNA Tests

Not covered / investigational:

Emerging assays: Donor-derived cell-free DNA tests with insufficient evidence of clinical validity (for example tests billed with 0118U or otherwise identified as emerging) are considered investigational for post-transplant management and are not covered.

Other Covered Lung Genetic Disorders

Covered when genetic testing is used to establish or confirm diagnosis to guide management and the member demonstrates clinical features consistent with the disorder:

Listed rare genetic lung disorders: Genetic testing to establish or confirm diagnosis of one of the following is considered medically necessary when clinical features consistent with the disorder are present: familial pulmonary fibrosis; primary ciliary dyskinesia; pulmonary lymphangioleiomyomatosis (LAM); pulmonary alveolar proteinosis (PAP).

Updated and New Criteria Sets

Policy updates include new and revised criteria sets for specific test types.

Donor-derived cfDNA for Lung Transplant Rejection: New criteria based on MolDX LCD L38582 govern donor-derived cell-free DNA testing for lung allograft rejection.

Refer to MolDX LCD L38582 for specific clinical indications and use prior authorization where required.

SERPINA1 Testing: Criteria for common variant analysis and sequencing/deletion-duplication analysis were updated to align with current guidelines and allow expanded coverage.

Known familial variant analysis criteria were moved to the General Approach to Genetic and Molecular Testing policy.

Donor-derived cell-free DNA (dd-cfDNA) assays that lack established clinical validity for post-transplant management are considered investigational and not covered. The policy specifies that tests with insufficient evidence (for example, those described under emerging evidence such as code 0118U) do not meet the threshold for coverage and may be denied when used to manage patients after lung transplantation.

The extracted sections do not list specific brand- or platform-level test exclusions. Coverage remains subject to the member’s plan terms, applicable state and federal requirements, and Health Plan administrative policies; any plan-level or regulatory exclusions take precedence over the criteria presented here.

SERPINA1 (alpha-1 antitrypsin) testing is considered medically necessary only for the indications explicitly listed in the policy and is investigational for all other indications. Similarly, dd-cfDNA testing is investigational when performed for indications outside the specified post-transplant criteria or when the assay’s clinical validity is not established.

This clinical policy provides guidance on medical necessity and is intended to assist in coverage determinations; it does not guarantee payment. Coverage and benefit administration remain subject to the member’s coverage document, applicable laws and regulations, and Health Plan administrative procedures.

Covered Indications

Coding and Billing

Example Covered CPT CodesCPTCovered

81332	SERPINA1 common variant analysis
81479	Unlisted molecular pathology procedure (used for sequencing and/or deletion/duplication analysis; also referenced for dd-cfDNA)
0118U	Emerging evidence donor-derived cell-free DNA assay (example)

Example Common ICD Codes for dd-cfDNAICD-10

T86.810	Lung transplant rejection
Z48.24	Encounter for aftercare following lung transplant
294.2	Code listed in document (as example ICD) — document source

Other Covered Disorders CPT RangeCPTCovered

81400-81408

Other covered lung disorder molecular pathology codes (range)

Referenced LCDmixed

L38582

MolDX: Molecular Testing for Solid Organ Allograft Rejection (LCD)

inv-14: AAT plasma level

Abnormally low (actionable)< 120 mg/dL

Borderline range90-140 mg/dL

Measurement method (reference)Plasma AAT measured via nephelometry (per ATS/ERS guidance)

inv-15: dd-cfDNA monitoring frequency

Default maximum monitoring interval (actionable)Not performed in the last 12 months — default frequency: once every 12 months

Precondition for repeat testingTest should not have been performed within prior 12 months to meet coverage criteria

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required per the Health Plan process for listed genetic tests where indicated. Examples of affected tests include SERPINA1 common variant analysis (CPT 81332) and sequencing and/or deletion/duplication analysis (CPT 81479), and donor-derived cell-free DNA tests where the payer requires prior authorization per applicable LCD (e.g., MolDX L38582). Providers should verify and complete any prior authorization or precertification steps before ordering tests.

Affected example CPT codes: 81332, 81479, 0118U (emerging dd-cfDNA)
Follow payer-specific prior authorization/process and local coverage determination requirements

Denial Risk

Investigational Indications May Be Denied

Tests ordered for indications that are not listed as medically necessary in this policy (for example, AATD testing or dd-cfDNA testing outside the specified criteria) are considered investigational and may be denied. Providers must ensure the clinical indication matches the medical necessity criteria in this policy before ordering.

Eligibility Requirements

No top-level eligibility requirement nodes were extracted for inclusion in this section.

Not Covered / Investigational

Donor-derived cfDNA assays and other genetic tests for which clinical validity or utility is insufficient are categorized as investigational and not covered. The policy states that assays lacking evidence (including those identified as emerging evidence) do not meet coverage thresholds for management after transplantation.

The document does not identify specific named genetic tests that are explicitly excluded; rather, noncoverage is determined by the evidence supporting the test and by member plan terms and applicable regulatory requirements.

Quick Provider Actions (Highlights)

Prior Authorization

Obtain prior authorization for listed CPTs (81332, 81479)

Ensure prior authorization is obtained per the Health Plan's process for the listed CPTs (e.g., 81332, 81479) before testing or billing.

Prior authorization applies to SERPINA1 testing codes and to 81479 when used for dd-cfDNA or sequencing/deletion-duplication services.

Prior Authorization

MolDX-aligned dd-cfDNA criteria may require prior authorization

Recognize that the new dd-cfDNA criteria aligned with MolDX LCD L38582 may trigger plan-level prior authorization requirements; follow plan-specific prior authorization rules.

Consult MolDX L38582 and the Health Plan prior authorization portal or contact the plan for authorization requirements.

Background

Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disorder characterized by reduced or dysfunctional alpha-1 antitrypsin protein leading to increased risk of lung and liver disease. Clinical features that prompt consideration of SERPINA1 genetic testing include abnormally low AAT plasma levels (below 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 without evident etiology, or a sibling with known AAT deficiency.

Definitions

inv-26: AATD — definition summary

Definition (concise)Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disorder causing low or dysfunctional AAT protein with increased risk of lung and liver disease.

Clinical features prompting testingEarly-onset emphysema (≤45 years), emphysema without other risk factors, basilar hyperlucency, unexplained liver disease, necrotizing panniculitis, C-ANCA–positive vasculitis, bronchiectasis without etiology, or sibling with known AAT deficiency.

Role of genetic testingGenetic testing of SERPINA1 (common variant analysis or sequencing/deletion-duplication) aids diagnosis and identifies at-risk relatives.

inv-27: dd-cfDNA — definition summary

Definition (concise)Donor-derived cell-free DNA (dd-cfDNA) is DNA from the transplanted organ measured in peripheral blood as a noninvasive biomarker to evaluate lung allograft rejection and adequacy of immunosuppression.

Policy Summary

PayerCentene

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

Policy CodePolicy N/A

Change TypeCriteria added and revised (AATD expandeddd-cfDNA new)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document transplant status and that dd-cfDNA was not performed in the prior 12 months when ordering donor-derived cfDNA testing.

SourceLink

On This Page

Note

Coverage Contingent on Plan Documents and LCD/NCDs

Coverage decisions are contingent on the member's specific coverage documents and any applicable national or local coverage determinations (NCDs/LCDs). Providers should confirm member eligibility, benefits, and any plan-level coverage limits prior to testing.

Coverage subject to Evidence of Coverage, Certificate of Coverage, policy contract, and Health Plan administrative policies
Applicable LCDs/NCDs (e.g., MolDX L38582) may impose additional requirements or restrictions

Documentation Required

Documentation and Medical Necessity

Providers must document clinical information that supports medical necessity. Documentation should be available in the medical record and submitted when requested as part of authorization or claims review.

For AATD testing: document serum/plasma AAT level (with numeric value and assay), clinical features (e.g., early-onset emphysema, unexplained liver disease, necrotizing panniculitis), age of onset, smoking and other risk factors, and relevant family history
For dd-cfDNA testing: document transplant status, date of transplantation, timing of prior dd-cfDNA testing (if any), current clinical signs/symptoms suggesting rejection, biopsy status/results (including if biopsy was inconclusive or contraindicated), and reason dd-cfDNA will inform management
Maintain records per Health Plan documentation and administrative policies; policy guidance does not guarantee payment

Step Therapy

Step Therapy Note

Step therapy is not applicable as a formal step-therapy requirement for donor-derived cfDNA testing in this policy. dd-cfDNA testing should be considered alongside other clinical assessments and biopsy status per the LCD and clinical criteria; a default monitoring frequency of up to once every 12 months is suggested when routine screening is performed without specific guideline-based intervals.

No explicit step-therapy sequence is specified; tests must meet medical necessity criteria
Default monitoring frequency (when applicable and not otherwise specified) is once every 12 months for post-transplant surveillance

Note

Provider Ordering and Genetic Counseling

Provider actions and ordering scope: dd-cfDNA tests are expected to be ordered by qualified physicians affiliated with a transplant center and used in conjunction with other clinical evaluations. Genetic counseling expectations follow the Health Plan's General Approach to Genetic and Molecular Testing policy where applicable.

Order dd-cfDNA testing in the context of post-transplant care and when it will impact clinical management
Follow the Health Plan's general genetic testing policy for counseling and related provider responsibilities