Table 2

Main DCM-causing genes

Gene	Mutation class	Functional effect	Phenotypic outcome
LMNA	Indel, truncating, aberrant splicing	GOF	More aggressive clinical decline culminating in SCD owing to malignant ventricular arrhythmias and end-stage HF.
MYBPC3	Indel, SNP, missense variants	GOF	Contractile deficiencies leading to severe mechanical stress and exacerbated cardiac myocyte apoptosis and necrosis inducing myocardial inflammation and severity of disease.
MYH7	SNP	LOF	Reduced contractility resulting from impaired sarcomere function.
PLN	Deletion (R14del+)	LOF	Reduced Ca2⁺ uptake in sarcolemma, desmosomal disassembly and increased cytoplasmic Ca2⁺ levels correlated with the presence of malignant ventricular arrhythmias and interstitial fibrosis.
RBM20	SNP, missense variant, frameshift	LOF	Impaired nuclear localisation of RBM20 protein leading to aberrant cytoskeleton assembly correlated with systolic dysfunction, LV dilatation and higher risk of ventricular arrhythmia.
TTN	SNP, Indel, frameshift, truncating, aberrant splicing	Haploinsufficiency, dominant negative	Disruption of sarcomere structure leading to cardiac dysfunction and remodelling.
TNNT2	Indel, SNP	LOF	Myofilament dysfunction mediated by significant increase in passive tension.
TNNI3	SNP, truncating	Haploinsufficiency, dominant negative	Myofilament dysfunction owing to increased Ca2⁺sensitivity and impaired length-dependent activation.

AD, autosomal dominant; DCM, dilated cardiomyopathy; GOF, gain of function; HF, heart failure; Indel, insertion and deletion; LMNA, lamin A/C; LOF, loss of function; MYBPC3, myosin-binding protein C3; MYH7, myosin-heavy chain 7; PLN, phospholamban; RBM20, RNA binding motif 20; SCD, sudden cardiac death; SNP, single nucleotide polymorphism; TNNI3, troponin I3 cardiac type; TNNT2, troponin T2 cardiac type; TTN, titin.