The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death.

ABSTRACT: There is an incomplete understanding of the burden of splice-disrupting variants in definitively associated inherited heart disease genes and whether these genes can amplify from blood RNA to support functional confirmation of splicing outcomes. We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. There was an excess burden of spli

SUBMITTER: Singer ES 

PROVIDER: S-EPMC10567745 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature