An assessment of the role of vinculin loss of function variants in inherited cardiomyopathy.

ABSTRACT: The ACMG/AMP variant classification framework was intended for highly penetrant Mendelian conditions. While it is appreciated that clinically relevant variants exhibit a wide spectrum of penetrance, accurately assessing and expressing the pathogenicity of variants with lower penetrance can be challenging. The vinculin (VCL) gene illustrates these challenges. Model organism data provide evidence that loss of function of VCL may play a role in cardiomyopathy and aggregate case-control studies suggest low penetrance. VCL loss of function variants, however, are rarely identified in affected probands and therefore there is a paucity of family studies clarifying the clinical significance of individual variants. This study, which aggregated data from >18,000 individuals who underwent gene panel o

SUBMITTER: Hawley MH 

PROVIDER: S-EPMC7714388 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature