Loss-of-Function FLNC Variants Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes When Identified Through Exome Sequencing of a General Clinical Population

TheFLNCgene has recently garnered attention as a likely cause of arrhythmogenic cardiomyopathy, considered an actionable genetic condition. However, the association with disease in an unselected clinical population is unknown. The study hypothesized that individuals with loss-of-function variants inFLNC(FLNCLOF) would have increased odds for arrhythmogenic cardiomyopathy-associated phenotypes versus variant-negative controls in the Geisinger MyCode cohort. FLNCLOFvariants are associated with increased odds of ventricular arrhythmia and dysfunction in an unselected clinical population. These findings support genomic screening ofFLNCfor actionable secondary findings.