Current evidence does not support genetic testing (SERPINA1 common variant analysis or sequencing and/or deletion/duplication analysis, diagnostic CFTR sequencing/deletion-duplication, or CFTR intron 9 polyT/TG analysis) for indications other than those specifically listed as medically necessary in this policy. Tests for alpha-1 antitrypsin deficiency, cystic fibrosis, and other rare lung disorders are covered only when the member meets the explicit clinical or laboratory criteria described in the respective sections of this policy.

Language that previously used the term 'Investigational' has been updated: where the document formerly labeled certain uses or tests as 'Investigational,' the policy now states that 'current evidence does not support' those uses. This change reflects a reframing of the evidence stance rather than addition of new medically necessary indications.

Use of SERPINA1 testing, diagnostic CFTR sequencing/deletion-duplication, or CFTR intron 9 polyT/TG analysis for any indications not explicitly enumerated in the relevant coverage sections is considered not supported by current evidence and therefore not consistent with medical necessity under this policy.

Where the policy indicates that 'current evidence does not support' a test (a phrasing that replaced 'Investigational'), those instances are treated as lacking sufficient evidence to meet medical necessity and may be managed accordingly by prior authorization and claims review processes.

This policy provides testing criteria for genetic disorders affecting the lungs, including diagnostic testing for alpha-1 antitrypsin deficiency (SERPINA1) and cystic fibrosis (CFTR), as well as guidance for genetic evaluation of certain rare lung disorders. Coverage criteria specify when sequencing, deletion/duplication, or CFTR intron polyT/TG testing are considered medically necessary and incorporate updated terminology and additional criteria moved into the Respiratory policy.

Eligibility for covered testing is defined by the medical necessity criteria in each section. Examples include: for SERPINA1 testing, an abnormally low AAT level (<120 mg/dL) or borderline level (90–140 mg/dL), early-onset emphysema (≤45 years), or emphysema without other risk factors; for diagnostic CFTR sequencing, a positive sweat chloride (≥60 mmol/L) or intermediate sweat chloride (30–59 mmol/L) with compatible clinical features, a positive newborn screen, or symptoms in at least two organ systems; and for CFTR intron 9 polyT/TG analysis, a diagnosis of cystic fibrosis combined with presence of an R117H variant.

Supplementary eligibility considerations referenced in the policy include documented clinical findings and laboratory results that support testing (for example, elevated immunoreactive trypsinogen on newborn screening, sweat chloride measurements, or characteristic multisystem features of cystic fibrosis). Family history (such as a sibling with known AAT deficiency or a first-degree relative with CF) is also recognized as supporting evidence within the specified criteria.

Testing for indications not explicitly described in this policy is considered unsupported by current evidence and is not covered. Providers must follow the policy’s specified clinical and laboratory criteria for SERPINA1, CFTR, and other listed lung disorder testing; orders outside those indications may be denied as not meeting medical necessity.

Tests or test uses that the policy now characterizes as 'current evidence does not support' (terms updated from 'Investigational') lack sufficient evidence for routine coverage and may be subject to denial or additional review under prior authorization procedures.