While the m6A-dependent and YTHDC1-guided Titin pre-mRNA splicing produced a shorter and more rigid Titin isoform, N2B, cardiomyocyte-targeted conditional YTHDC1 knockout led to expression dominance of longer and less stiff N2BA isoform manifesting with DCM phenotype and ultimately HF.150. Here, YTHDC1 is linked to familial dilated cardiomyopathy.