ModifiedCentenePolicy N/A

Concert Genetic Testing: Lung Disorders (SERPINA1 and donor-derived cfDNA)

Coverage criteria for genetic and molecular tests to diagnose inherited lung disorders (notably alpha-1 antitrypsin deficiency) and use of donor-derived cell-free DNA for monitoring lung transplant rejection for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyGenetic testing for lung disorders (SERPINA1 and donor-derived cfDNA)

Policy CodePolicy N/A

Change TypeMaterial revisions and additions (criteria updates, new dd-cfDNA rules)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization when plan rules apply; ensure dd-cfDNA testing has not been performed in the prior 12 months and documents meet specified post‑transplant indications.

SourceLink

POLICY UPDATE CHANGES

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

Donor-derived cell-free DNA tests for lung transplant rejection (evidence-based tests) listed as medically necessary under defined post-transplant conditions with a default maximum frequency of once every 12 months.

Updated title to reflect V1.2024, V2.2024, and V1.2025 versions; overview, coding, reference table, background and references updated.

New Evidence-Based and Emerging Evidence criteria for donor-derived cell-free DNA for lung transplant rejection created.

81332,81479,0118URepresentative CPT codes referenced

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 / Sequencing/Deletion-Duplication — Initial diagnostic testing

SERPINA1 testing (81332 or 81479) is medically necessary when ALL of the following apply:

SERPINA1 diagnostic criteria

Indications: 1. Abnormally low (<120 mg/dL) OR borderline (90-140 mg/dL) AAT level measured by nephelometry; 2. Early-onset emphysema (45 years of age or younger); 3. Emphysema in the absence of additional risk factors (eg, 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. A sibling with known AAT deficiencyN/A
If none of these indications are present, testing is investigational.

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

Evidence-based dd-cfDNA testing (81479) is medically necessary when ALL of the following are met:

dd-cfDNA evidence-based criteria

Required preconditions: A. Member has undergone lung transplantation AND B. The test has not been performed in the last 12 monthsN/A
Both A and B required
Clinical scenarios: 1. Clinical signs of acute rejection; OR 2. A biopsy was performed and is inconclusive for rejection; OR 3. Monitoring for adequacy of immunosuppressionN/A
At least one scenario must be met

Emerging Evidence Donor-Derived Cell-free DNA

Emerging evidence dd-cfDNA tests (e.g., 0118U) are:

Emerging tests: Considered investigational due to insufficient established clinical validity/utilityN/A

Not covered

Other Covered Genetic Lung Disorders

Other covered lung disorders:

Rare genetic lung disorders: Genetic testing to establish or confirm diagnosis is medically necessary when the member demonstrates clinical features consistent with the disorderN/A

Examples include familial pulmonary fibrosis, primary ciliary dyskinesia, pulmonary lymphangioleiomyomatosis (LAM), and pulmonary alveolar proteinosis (PAP); other disorders evaluated per General Approach policy

Notable criteria updates (partial capture)

Revisions noted to existing SERPINA1 and donor-derived cfDNA criteria

SERPINA1 criteria updated: SERPINA1 Common Variant Analysis or Sequencing and/or Deletion/Duplication Analysis criteria were updated to better align with current guidelines and expanded coverage.

Full criteria relocated or updated elsewhere in the policy document.

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

See the general approach policy for consolidated criteria.

Donor-derived cfDNA criteria added: New Evidence-Based and Emerging Evidence criteria sets were created for donor-derived cell-free DNA for lung transplant rejection based on CMS/MolDX LCD guidance.

Full criteria text present elsewhere in this policy; Emerging Evidence set addresses tests lacking established clinical validity (eg, 0118U).

SERPINA1 testing for indications other than the listed clinical features is considered investigational. The policy's SERPINA1 criteria specify that common variant analysis (CPT 81332) or sequencing and/or deletion/duplication analysis (CPT 81479) is medically necessary only when the member meets one of the enumerated indications (for example: an abnormally low AAT level < 120 mg/dL, early-onset emphysema ≤45 years, unexplained liver disease, necrotizing panniculitis, C-ANCA positive vasculitis, bronchiectasis without evident etiology, or a sibling with known AAT deficiency). All other indications for SERPINA1 testing are investigational.

Coverage decisions under this clinical policy are subject to the terms, conditions, exclusions, and limitations of the applicable health plan coverage documents and to state and federal requirements. Where there is a conflict between this policy and state Medicaid provisions, the state Medicaid provisions take precedence.

Donor-derived cell-free DNA assays that lack established clinical validity are classified as Emerging Evidence and are considered investigational. The policy includes an Emerging Evidence category (example CPT 0118U) for dd-cfDNA tests without sufficient evidence of clinical validity; such tests are not covered pending demonstration of clinical validity and utility.

This section of the document summarizes investigational determinations but does not list every possible 'not medically necessary' scenario. For complete statements of conditions deemed not medically necessary, providers should refer to the full policy text and applicable coverage documents.

Coding and Billing

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 for sequencing and/or deletion/duplication analysis and some dd-cfDNA tests)

Emerging Evidence dd-cfDNACPTExperimental

0118U

Emerging evidence donor-derived cell-free DNA for lung transplant rejection

Example ICD-10 CodesICD-10

E88.01

Alpha-1 antitrypsin deficiency

ICD-10 Codes Related to TransplantICD-10

T86.810	Lung transplant rejection
Z48.24	Encounter for aftercare following lung transplant
Z94.2	Lung transplant status

Reference table additionsICD-10

E88.01

Added under SERPINA1 Common Variant reference table

Alpha-1 antitrypsin plasma level reference values

Abnormally low (actionable)< 120 mg/dL (alpha-1 antitrypsin plasma level measured by nephelometry)

Borderline range90-140 mg/dL (borderline normal AAT level)

Normal range (reference)Approximately 83/120 - 200/220 mg/dL as reported by ATS/ERS

dd-cfDNA test frequency default maximum (12 months)

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

Covered Indications

Diagnosis of alpha-1 antitrypsin deficiency (AATD) when member meets any listed clinical features or abnormal AAT levels

AATD diagnostic indications

Clinical/lab features: Abnormally low (<120 mg/dL) or borderline (90-140 mg/dL) AAT level by nephelometry; Early-onset emphysema (<=45 years); Emphysema without additional risk factors; Emphysema with prominent basilar hyperlucency; Unexplained liver disease; Necrotizing panniculitis; C-ANCA positive vasculitis (granulomatosis with polyangiitis); Bronchiectasis without evident etiology; A sibling with known AAT deficiencyN/A
If none present, testing is investigational.

Monitoring or evaluation for lung allograft rejection in lung transplant recipients meeting specified conditions

dd-cfDNA monitoring criteria

Eligibility Requirements

Eligibility for SERPINA1 genetic testing requires that the member meet one of the policy-specified clinical indications. Examples that establish eligibility include: an abnormally low AAT plasma level (< 120 mg/dL) or borderline levels (90–140 mg/dL), early-onset emphysema (≤45 years), emphysema without other risk factors, prominent basilar hyperlucency on imaging, unexplained liver disease, necrotizing panniculitis, C-ANCA positive vasculitis, bronchiectasis of unclear etiology, or a sibling with known AAT deficiency.

Eligibility for evidence-based donor-derived cell-free DNA testing (CPT 81479) requires that the member has undergone lung transplantation and that the test has not been performed in the prior 12 months. Additionally, one of the specified clinical scenarios must be met: clinical signs of acute rejection, an inconclusive biopsy, or monitoring for adequacy of immunosuppression.

Tests in the Emerging Evidence dd-cfDNA category are not eligible for coverage because they lack demonstrated clinical validity. The policy explicitly considers such tests investigational (example CPT 0118U) and therefore not covered.

Genetic testing to diagnose or confirm rare inherited lung disorders (for example, familial pulmonary fibrosis, primary ciliary dyskinesia, lymphangioleiomyomatosis, pulmonary alveolar proteinosis) is eligible when the member presents clinical features consistent with the disorder; testing decisions for these rare conditions should follow the General Approach policy and disease-specific guidance.

Provider Actions and Responsibilities

Prior Authorization

Prior Authorization Required

Prior authorization is required for SERPINA1 genetic testing (CPT 81332, 81479) and donor‑derived cell‑free DNA testing (CPT 81479) as applicable. Providers must obtain plan authorization before testing per the member's benefit plan and administrative policies.

Affected codes: SERPINA1 common variant analysis (81332); sequencing/deletion‑duplication analysis (81479); donor‑derived cfDNA (81479).
Obtain prior authorization from the member's Health Plan before ordering when the test is being requested for coverage consideration.

Note

Coverage Decision Constraints

Coverage is determined by the medical necessity criteria in this policy and is subject to the terms, conditions, exclusions, and limitations of the member's coverage documents. Decisions may also be informed by applicable CMS NCDs/LCDs and Health Plan administrative policies.

Coverage is contingent on the member's specific benefit plan and may vary by product (e.g., Medicare, Medicaid, commercial).

Not Covered / Investigational

Donor-derived cfDNA tests developed using algorithmic methods or otherwise lacking established clinical validity are considered not covered under the Emerging Evidence designation. The policy notes that new Emerging Evidence criteria were created for tests without established clinical validity and that such tests (e.g., CPT 0118U) are investigational until validity and utility are demonstrated.

Emerging Evidence criteria apply to algorithmic or novel dd-cfDNA tests when clinical validity has not been established. The intended clinical uses addressed by evidence-based criteria—such as assisting evaluation of immunosuppression adequacy, using the test as a rule-out for acute rejection, evaluating allograft status after a physician-assessed pretest probability, or assessing inconclusive biopsy results—must be supported by validation data; in the absence of such data, algorithmic or other novel tests remain investigational.

Background

Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disorder caused by pathogenic variants in SERPINA1 that result in reduced or dysfunctional alpha-1 antitrypsin protein and an increased risk of lung and liver disease. Clinical features that should prompt evaluation include early-onset emphysema (≤45 years), emphysema without recognized risk factors, prominent basilar hyperlucency on imaging, unexplained liver disease, necrotizing panniculitis, anti-proteinase 3 (C-ANCA) positive vasculitis, bronchiectasis without an evident cause, and relevant family history; plasma AAT measured by nephelometry with levels < 120 mg/dL (abnormally low) or borderline (90–140 mg/dL) warrants genetic testing consideration.

Definitions

Definition — Alpha-1 antitrypsin deficiency (AATD)

Definition (actionable)Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disorder resulting in decreased production or dysfunctional alpha-1 antitrypsin protein, increasing risk for lung and liver disease

Clinical relevanceGenetic testing (SERPINA1) aids diagnosis, directs treatment, and identifies at-risk family members

Typical triggers for testingAbnormally low or borderline AAT levels, early-onset emphysema, unexplained liver disease, necrotizing panniculitis, C-ANCA positive vasculitis, bronchiectasis without etiology, or a sibling with known AAT deficiency

Definition — Donor-derived cell-free DNA (dd-cfDNA)

Definition (actionable)Donor-derived cell-free DNA (dd-cfDNA) is circulating donor-origin DNA measured in peripheral blood to help detect allograft injury or rejection after lung transplantation

Revision History

2024-11revisionLatest

Semi-annual review; updated title to V1.2025 and added new Evidence-Based and Emerging Evidence criteria for donor-derived cell-free DNA for lung transplant rejection based on LCD guidance.

2024-04revision

Semi-annual review; updated title to V2.2024 and revised SERPINA1 Common Variant and Sequencing/Deletion-Duplication criteria to better align with current guidelines, expanding coverage and moving Known Familial Variant Analysis to the General Approach policy.

2023-10revision

Policy Summary

PayerCentene

PolicyGenetic testing for lung disorders (SERPINA1 and donor-derived cfDNA)

Policy CodePolicy N/A

Change TypeMaterial revisions and additions (criteria updates, new dd-cfDNA rules)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization when plan rules apply; ensure dd-cfDNA testing has not been performed in the prior 12 months and documents meet specified post‑transplant indications.

SourceLink

On This Page

Diagnosis/confirmation of rare genetic lung disorders when clinical features consistent

Rare genetic lung disorder criteria: Genetic testing to establish or confirm diagnosis is considered medically necessary when the member demonstrates clinical features consistent with the disorderN/A

Examples: familial pulmonary fibrosis; primary ciliary dyskinesia; pulmonary lymphangioleiomyomatosis (LAM); pulmonary alveolar proteinosis (PAP). Clinical features may be defined in GeneReviews, OMIM, or other scholarly sources.

Donor-derived cell-free DNA testing for lung transplant rejection — Evidence-Based and Emerging Evidence criteria

Evidence-based dd-cfDNA: Peripheral blood dd-cfDNA tests with established clinical validity/utility (81479) are medically necessary when the member is a lung transplant recipient, the test has not been performed in the last 12 months, and at least one clinical scenario is present (clinical signs of acute rejection; inconclusive biopsy; monitoring adequacy of immunosuppression).N/A

Testing outside these indications is investigational.

Emerging dd-cfDNA: dd-cfDNA tests with insufficient evidence of clinical validity (eg, 0118U) are considered investigational and not medically necessary.N/A

Refer to Emerging Evidence criteria set.

Denial Risk

Denial Triggers

Tests will be denied when submitted documentation does not meet the policy clinical criteria or when testing is performed more frequently than allowed (e.g., dd‑cfDNA within 12 months without meeting interval exceptions). Lack of prior authorization when required is also a basis for denial.

Denial triggers include: insufficient or missing clinical indications that meet policy criteria; dd‑cfDNA performed within 12 months without documented exception; absence of required prior authorization; testing for indications considered investigational by this policy.

Documentation Required

Required Supporting Clinical Documentation

Providers must supply supporting clinical documentation with test requests to demonstrate that policy criteria are met. For SERPINA1 testing include plasma AAT level results and relevant clinical features; for dd‑cfDNA include transplant history, timing of prior dd‑cfDNA (if any), clinical signs or biopsy results prompting testing, and the intended clinical use.

SERPINA1: document plasma alpha‑1 antitrypsin level (nephelometry) with value and date; age of onset (e.g., emphysema ≤45 years); absence of alternate risk factors (e.g., smoking); family history (sibling with known AATD) or other listed clinical features.
dd‑cfDNA: document lung transplant status, date of transplant, date of last dd‑cfDNA test (if any), specific clinical indication (signs of acute rejection, inconclusive biopsy, or monitoring adequacy of immunosuppression), and the planned clinical action resulting from the test.
When genetic testing is considered, document that genetic counseling was offered or provided as appropriate.

Documentation Required

Provider Responsibilities and Documentation Context

Providers are responsible for ordering tests consistent with scope-of-practice and evidence-based guidance. For dd‑cfDNA, orders should come from qualified physicians affiliated with a transplant center and include documentation per CMS LCD guidance. Providers must follow all plan administrative policies and consult applicable NCDs/LCDs prior to ordering.

Ensure ordering clinician credentials and transplant center affiliation are documented for dd‑cfDNA testing.
Include the clinical rationale and how results will impact management (e.g., to rule out AR, to decide on biopsy, to adjust immunosuppression).
Adhere to plan submission requirements for prior authorization, appeals, and medical record retention.

Step Therapy

Step Therapy / Sequencing

No formal step‑therapy or sequencing requirements are imposed by this policy; however, tests should be used in the sequence supported by evidence and guideline recommendations. For example, dd‑cfDNA may be used as a noninvasive alternative to biopsy when appropriate per LCD guidance, and SERPINA1 testing is indicated after abnormal or borderline AAT levels or compatible clinical features.

dd‑cfDNA: default frequency for monitoring in the absence of specific guideline regimens is once every 12 months unless clinical indication justifies sooner testing.
SERPINA1: testing usually follows abnormal/borderline plasma AAT measurement or presence of listed clinical features rather than requiring other genetic tests first.

Note

Operational Provider Actions

Providers should review this policy in conjunction with the medical necessity criteria sections for SERPINA1 and dd‑cfDNA testing to ensure all required elements are present prior to submission. Failure to include necessary documentation or to follow plan-level administrative procedures may delay authorization or result in denial.

Confirm that the requested test indication matches one of the policy's listed medically necessary criteria.
Attach pertinent clinical notes, lab values, biopsy reports (if performed), and prior authorization forms as required.
Contact the Health Plan's provider services or prior authorization department for any questions about documentation or submission procedures.