Abstract Titin, encoded by the TTN gene, is the largest human protein, essential for maintaining muscle cell stability and regulating myocardial contraction. TTN truncating variants (TTNtv) have emerged as the most common genetic cause of dilated cardiomyopathy (DCM), accounting for up to 25% of familial cases and 18% of sporadic cases. This review examines the complex relationship between TTN variants and DCM, highlighting the challenges posed by incomplete penetrance and variable expressivity. While truncating variants primarily in the A-band region […]