Functional Assays Are Essential for Interpretation of Missense Variants Associated with Variable Expressivity.

ABSTRACT: Missense DNA variants have variable effects upon protein function. Consequently, interpreting their pathogenicity is challenging, especially when they are associated with disease variability. To determine the degree to which functional assays inform interpretation, we analyzed 48 CFTR missense variants associated with variable expressivity of cystic fibrosis (CF). We assessed function in a native isogenic context by evaluating CFTR mutants that were stably expressed in the genome of a human airway cell line devoid of endogenous CFTR expression. 21 of 29 variants associated with full expressivity of the CF phenotype generated <10% wild-type CFTR (WT-CFTR) function, a conservative threshold for the development of life-limiting CF lung disease, and five variants had moderately decreased funct

SUBMITTER: Raraigh KS 

PROVIDER: S-EPMC5992123 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature