Asnoted in “Materials and methods,” clinical sensitivity of NGS + CNV is expectedto exceed that of CF23; therefore, the clinical validity assessment focused onvariant classification specificity because it has been directly questioned andwas as-yet unestablished.19 We leveraged the CFTR2 database as atruth set because it is based on over 89,000 diagnosed CF patients with knownsequencing results and augments patient-level clinical data with in vitro data;accordingly, it is the gold standard of CFTR variant interpretations(pathogenic, uncertain significance [VUS], or variable). The gene discussed is CFTR; the disease is cystic fibrosis.