TTN Truncating Variants in DCM — EECC MCQ

Correct answer: C — TTN truncating variants are the most common genetic cause of DCM (15-25% of familial DCM), generally associated with a moderate arrhythmic risk that follows standard LVEF-based ICD criteria (unlike high-risk LMNA/FLNC variants); TTNtv carriers may have better response to GDMT with higher rates of LVEF recovery

Titin (TTN) truncating variants are the most frequently identified genetic cause of DCM, found in: ~15-25% of familial DCM, ~10% of sporadic DCM, and ~10% of peripartum cardiomyopathy. Key features: (1) TTNtv is a common DCM genotype with MODERATE arrhythmic risk — unlike LMNA/FLNC/PLN/RBM20 which are classified as 'arrhythmogenic genotypes', TTNtv generally follows standard LVEF-based ICD criteria (≤35%); (2) TTNtv carriers may have higher rates of LVEF recovery with GDMT (potentially favourable prognosis); (3) the 2023 ESC Cardiomyopathy Guidelines distinguish TTNtv from the high-risk arrhythmogenic genotypes for ICD decision-making. However, interpretation requires caution: TTN is a very large gene with background truncating variants in 1-3% of the general population — clinical context, variant location (A-band truncations are most pathogenic), and segregation analysis are needed.

Reference: ESC (2023): Cardiomyopathies Guidelines