CurrentWellCarePolicy N/A

Genetic Testing: Lung Disorders (SERPINA1 / AATD and other genetic lung disorders)

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Defines medical necessity criteria for genetic testing of alpha-1 antitrypsin deficiency (SERPINA1) and guidance for testing other rare genetically-associated lung disorders; applies to providers requesting genetic tests for WellCare members.

Policy Summary

PayerWellCare

PolicyGenetic Testing: Lung Disorders (SERPINA1 / AATD and other genetic lung disorders)

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateN/A

Last ReviewOct 1, 2023

Next Review DateMar 23, 2024

Key ActionDocument serum alpha-1 antitrypsin level (nephelometry) and relevant family history when requesting genetic testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

SERPINA1 testing specifiedSERPINA1 testing specified

AAT thresholdsAAT level thresholds

Other lung disordersList of other disorders

CPT examplesRelevant CPT examples

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CurrentWellCarePolicy N/A

Genetic Testing: Lung Disorders (SERPINA1 / AATD and other genetic lung disorders)

Customize your policy alerts

Sign up for all WellCare policy alerts

Know when WellCare releases new policies or updates existing guidance.

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Policy Summary

PayerWellCare

PolicyGenetic Testing: Lung Disorders (SERPINA1 / AATD and other genetic lung disorders)

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateN/A

Last ReviewOct 1, 2023

Next Review DateMar 23, 2024

Key ActionDocument serum alpha-1 antitrypsin level (nephelometry) and relevant family history when requesting genetic testing.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

SERPINA1 testing specifiedSERPINA1 testing specified

AAT thresholdsAAT level thresholds

Other lung disordersList of other disorders

CPT examplesRelevant CPT examples

Coverage Criteria for Genetic Testing

SERPINA1 Known Familial Variant Analysis

Covered when ALL of the following are met:

Familial targeted testing: Member has a close relative with a known pathogenic or likely pathogenic variant in SERPINA1.

Targeted variant analysis CPTs 81332, 81403 are considered medically necessary in this circumstance.

SERPINA1 common variant analysis or sequencing/deletion-duplication

Covered when ALL of the following are met:

Lab criterion: Member has abnormally low (<120 mg/dL) or borderline (90-140 mg/dL) alpha-1 antitrypsin level measured by nephelometry.<120 mg/dL or 90-140 mg/dL

AAT level must be measured by nephelometry and documented.

Clinical features (at least one): One of: early-onset emphysema (45 years of age or younger); emphysema in the absence of additional risk factors (e.g., smoking, occupational dust exposure); emphysema with prominent basilar hyperlucency; otherwise unexplained liver disease; necrotizing panniculitis; C-ANCA positive vasculitis (granulomatosis with polyangiitis); bronchiectasis without evident etiology; or a sibling with known AAT deficiency.

If these conditions are met, common variant analysis (81332) or sequencing/deletion-duplication (81479) is considered medically necessary.

Other Covered Lung Disorders

Covered when ALL of the following are met:

Clinical features consistent with disorder: Genetic testing to establish or confirm diagnosis of a listed rare genetic lung disorder (for example: familial pulmonary fibrosis, primary ciliary dyskinesia, pulmonary lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP)).

Member must demonstrate clinical features consistent with the specific disorder; clinical features may be referenced from resources such as GeneReviews, OMIM, or Genetics Home Reference.

Targeted familial SERPINA1 testing (CPT codes 81332, 81403) is considered investigational when the request is for any indication other than testing a member who has a close relative with a known pathogenic or likely pathogenic SERPINA1 variant. The policy specifies that the familial targeted pathway is medically necessary only when a close relative with a reported pathogenic/likely pathogenic SERPINA1 variant is documented; all other indications for targeted familial variant analysis are investigational.

Any SERPINA1 genetic testing performed outside the policy’s defined familial or diagnostic pathways is considered investigational. Specifically, requests for targeted familial variant analysis without a documented close relative with a known pathogenic or likely pathogenic SERPINA1 variant, and requests for common variant analysis, sequencing or deletion/duplication (e.g., CPT 81332, 81479) that do not meet the stated alpha-1 antitrypsin laboratory thresholds and clinical feature criteria, will be treated as investigational.

Diagnosis of AATD and related testing guidance

Guidance for diagnosing AATD and related testing pathways:

AATD diagnostic threshold: Alpha-1 antitrypsin level measured by nephelometry is abnormally low (<120 mg/dL) or borderline (90-140 mg/dL).<120 mg/dL or 90-140 mg/dL

AAT levels should be documented in supporting clinical information when pursuing genetic testing for AATD.

Clinical features: At least one clinical feature such as early-onset emphysema (<=45 years), emphysema without additional risk factors, emphysema with prominent basilar hyperlucency, otherwise unexplained liver disease, necrotizing panniculitis, C-ANCA positive vasculitis (granulomatosis with polyangiitis), bronchiectasis without evident etiology, or a sibling with known AAT deficiency.

These features align with guidance cited in the policy and support proceeding with common variant analysis or sequencing/Del/Dup testing.

Familial targeted testing when close relative affected: Testing is appropriate when a close relative (first-, second-, or third-degree) has a known pathogenic or likely pathogenic SERPINA1 variant.

Relevant Codes and Laboratory Thresholds

Referenced CPT Codes for SERPINA1 testingCPT

81332	Targeted variant analysis / common variant analysis (as referenced for SERPINA1)
81403	Targeted familial variant analysis (as referenced for SERPINA1 known familial variant analysis)
81479	Unlisted molecular pathology procedure (referenced for sequencing and/or deletion/duplication analysis for SERPINA1)

Referenced ICD-10ICD-10

E88.01

Alpha-1 antitrypsin deficiency (added to policy reference table)

Alpha-1 antitrypsin level (nephelometry) thresholds

Abnormally low (actionable)Less than 120 mg/dL (measured by nephelometry)

Borderline90-140 mg/dL (measured by nephelometry)

Normal range (reference)Approximately 120-220 mg/dL depending on lab reference (ATS/ERS notes normal ~83/120 - 200/220 mg/dL)

Provider Actions, Documentation, and Billing Notes

Prior Authorization

Prior authorization and coding may be required

Prior authorization may be required for the listed Concert Genetics SERPINA1 tests and associated CPT codes (e.g., 81332, 81403, 81479). Providers should reference the Concert Genetics platform and payer coding guidance prior to claim submission.

Referenced CPT examples in policy: 81332, 81403, 81479
Check Concert Genetics test listing for specific registered test names and CPT mapping

Note

Order using the correct testing pathway and document indication

When ordering SERPINA1 testing, document the clinical indication and ensure the request follows the appropriate pathway (familial known-variant vs diagnostic). For familial targeted testing, include evidence of a close relative's known pathogenic/likely pathogenic SERPINA1 variant; for diagnostic testing, include AAT level and at least one qualifying clinical feature per policy.

Select targeted familial variant analysis (81332, 81403) only when a close relative has a known pathogenic/likely pathogenic SERPINA1 variant

Covered Indications and Clinical Context

Clinical features guidance and testing thresholds for AATD and related disorders

Clinical and testing guidance to support coverage determinations:

AAT level measurement: Alpha-1 antitrypsin level should be measured by nephelometry and documented; thresholds used in the policy are abnormally low (<120 mg/dL) or borderline (90-140 mg/dL).<120 mg/dL or 90-140 mg/dL

Documented AAT level is expected prior to sequencing unless familial known-variant pathway is used.

When to use targeted familial testing: Use targeted familial variant analysis (81332, 81403) when a close relative has a known pathogenic or likely pathogenic SERPINA1 variant.

Requests for familial targeted testing without a close relative with a known pathogenic/likely pathogenic variant will be considered investigational and may be denied.

When to pursue sequencing/Del/Dup or common variant analysis:

Eligibility Requirements

Eligibility determinations for SERPINA1 testing follow the policy’s specified clinical and familial pathways. For targeted familial variant analysis, eligibility requires documentation of a close relative with a known pathogenic or likely pathogenic SERPINA1 variant. For diagnostic genetic testing (common variant analysis, sequencing, or deletion/duplication), eligibility requires documented alpha-1 antitrypsin level by nephelometry meeting the policy thresholds and at least one of the listed clinical features consistent with AAT deficiency.

Additional eligibility considerations include documentation expectations: alpha-1 antitrypsin level results should be provided when used to justify testing, and the family-history relationship (first-, second-, or third-degree) should be specified when requesting familial targeted analysis. Requests lacking required laboratory or family-history documentation may be denied as investigational.

Not Covered / Investigational

SERPINA1 testing is not covered (considered investigational) when the member does not meet the policy criteria for either pathway. This includes: absence of a close relative with a known pathogenic/likely pathogenic SERPINA1 variant for targeted familial variant analysis, or failure to document an alpha-1 antitrypsin level by nephelometry meeting the policy thresholds (abnormally low <120 mg/dL or borderline 90–140 mg/dL) plus at least one qualifying clinical feature for diagnostic sequencing/common-variant testing.

Definitions

Close relatives defined (examples)

First-degree relativesParents, siblings, and children

Second-degree relativesGrandparents, aunts, uncles, nieces, nephews, grandchildren, and half-siblings

Third-degree relativesGreat-grandparents, great aunts/uncles, great-grandchildren, and first cousins

Background

Alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive condition caused by decreased or dysfunctional alpha-1 antitrypsin protein that increases risk for lung and liver disease. Genetic testing of SERPINA1 helps establish diagnosis, guide management, and identify at-risk family members. The policy uses laboratory cutoffs measured by nephelometry—individuals with abnormally low (<120 mg/dL) or borderline (90–140 mg/dL) AAT levels should be evaluated further. Clinical features that raise suspicion and support diagnostic testing include: early-onset emphysema (≤45 years), emphysema without typical risk factors (e.g., smoking), emphysema with basilar hyperlucency, otherwise unexplained liver disease, necrotizing panniculitis, C-ANCA positive vasculitis (granulomatosis with polyangiitis), bronchiectasis without an evident etiology, or a sibling with known AAT deficiency. The policy also defines close relatives as first-, second-, and third-degree blood relatives for the familial testing pathway.

Policy Summary

PayerWellCare

PolicyGenetic Testing: Lung Disorders (SERPINA1 / AATD and other genetic lung disorders)

Policy CodePolicy N/A

Change TypeNo material clinical or coverage changes

Effective DateN/A

Last ReviewOct 1, 2023

Next Review DateMar 23, 2024

Key ActionDocument serum alpha-1 antitrypsin level (nephelometry) and relevant family history when requesting genetic testing.

SourceLink

On This Page

In this circumstance, targeted familial variant analysis (81332, 81403) is considered medically necessary.

Testing for other rare genetic lung disorders: Genetic testing to establish or confirm diagnoses of rare genetic lung disorders (familial pulmonary fibrosis, primary ciliary dyskinesia, LAM, PAP) is appropriate when clinical features consistent with the disorder are present.

Clinical features may be referenced from GeneReviews, OMIM, or similar resources; consideration follows the General Approach to Genetic and Molecular Testing when not covered explicitly.

Select common variant analysis (81332) or sequencing/Del/Dup (81479) when AAT level thresholds and clinical features are met

Documentation Required

Provide AAT level (with value) and detailed family relationship

Include serum alpha-1 antitrypsin level measured by nephelometry with the numeric result when available, and a detailed family history specifying whether the affected relative is first-, second-, or third-degree when familial testing is requested.

AAT level: note if <120 mg/dL (abnormally low) or 90–140 mg/dL (borderline) as measured by nephelometry
Family history must state degree of relationship (first-, second-, or third-degree) to the relative with the known SERPINA1 variant

Denial Risk

Missing family or lab/clinical documentation may trigger denial

Requests for targeted familial SERPINA1 testing (81332, 81403) that do not document a close relative with a known pathogenic or likely pathogenic SERPINA1 variant, or diagnostic testing that lacks required AAT level and qualifying clinical features, may be considered investigational and denied.

Familial pathway will be considered investigational if no close relative with known pathogenic/likely pathogenic SERPINA1 variant is documented
Common variant/sequencing requests without AAT level <120 mg/dL or 90–140 mg/dL borderline plus at least one listed clinical feature may be denied

Note

Order via Concert Genetics platform and follow payer/process guidance

Use the Concert Genetics ordering platform and follow payer/process guidance for test selection and submission; consult the Concert Genetics test registry for the comprehensive list of registered tests and CPT mappings prior to ordering.

Reference Concert Genetics platform for registered test names and to confirm CPT mappings
Follow payer coding guidance prior to claim submission

Step Therapy

Supplemental ordering checklist and documentation to reduce denials

Supplemental actions: verify prior authorization requirements and CPT code selection, attach AAT nephelometry result and clinical notes documenting at least one qualifying clinical feature (if using diagnostic pathway), and clearly state the degree of relatedness when ordering familial testing.

Confirm whether prior authorization is required for the chosen CPT (81332, 81403, 81479)
Attach AAT level (nephelometry) result and clinical documentation of qualifying features (e.g., early-onset emphysema, unexplained liver disease) for diagnostic pathway
Document degree of relationship to affected relative for familial targeted testing

Pursue SERPINA1 common variant analysis (81332) or sequencing/deletion-duplication (81479) to establish diagnosis when documented AAT level criteria are met AND at least one listed clinical feature is present.

Testing outside these stated diagnostic or familial criteria is considered investigational / not medically necessary.

Documentation requirements: Supporting documentation should include serum AAT level with value (nephelometry) when available and a family history specifying degree of relatedness when familial testing is requested.

Lack of documented AAT level or close relative with known pathogenic SERPINA1 variant are potential denial triggers for SERPINA1 testing.