查看文章

Background

Truncating TTN variants (TTNtv) cause DCM and arrhythmias and are recommended for return as secondary genomic findings, but findings from clinically ascertained cohorts are unclear on TTNtv-associated risks by location. With a∼ 1% TTNtv population prevalence, accurate risk prediction is essential to guide appropriate management, particularly in asymptomatic patients and family members.

Objective

To characterize the TTNtv-associated arrhythmia burden by variant location in a rural healthcare population.

Methods

Geisinger’s MyCode® Community Health Initiative pairs electronic health records with exome data. High quality TTNtv were selected based on allele frequency (< 0.01) and molecular consequence, stratified by protein region (Z-disc, I-band [proximal/distal], A-band, and M-band). Arrhythmia related diagnoses were compared to the rest of MyCode using Firth’s bias-reduced logistic …