Abstract 20814: High Rate of Atrial Arrhythmias in Individuals With Truncating Titin Mutations Including the First Dilated Cardiomyopathy Related Titin Founder Mutation

Introduction: Truncating TTN variants (TTNtv) play an important role in the development of dilated cardiomyopathy (DCM). We collected evidence for the pathogenicity of TTN c.59926+1Gu003eA, studied its founder effect and describe the associated phenotype including the presence of (paroxysmal) atrial fibrillation ((p)AF) and also evaluated this in carriers of other TTNtv. Methods: Clinical and genetic data from 11 probands and 19 family members with the TTN c.59926+1Gu003eA variant were collected. We studied the founder effect by haplotype analysis and genealogy. We calculated the combined logarithm of the odds (LOD) score taking a penetrance of 80% into account. The presence of DCM and (p)AF) was further studied in 53 carriers of 16 other TTNtv. Results: TTN c.59926+1Gu003eA: Haplotype analysis revealed a 4 Mb shared region, indicating a common ancestor. Genealogy going back five to nine generations revealed three pairs of common ancestors. Segregation analysis yielded a combined LOD score of 3.6. DCM was the predomi...