Table 2

Main DCM-causing genes

GeneMutation classFunctional effectPhenotypic outcome
LMNA Indel, truncating, aberrant splicingGOFMore aggressive clinical decline culminating in SCD owing to malignant ventricular arrhythmias and end-stage HF.
MYBPC3 Indel, SNP, missense variantsGOFContractile deficiencies leading to severe mechanical stress and exacerbated cardiac myocyte apoptosis and necrosis inducing myocardial inflammation and severity of disease.
MYH7 SNPLOFReduced contractility resulting from impaired sarcomere function.
PLN Deletion
(R14del+)
LOFReduced 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, frameshiftLOFImpaired 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 splicingHaploinsufficiency,
dominant negative
Disruption of sarcomere structure leading to cardiac dysfunction and remodelling.
TNNT2 Indel, SNPLOFMyofilament dysfunction mediated by significant increase in passive tension.
TNNI3 SNP, truncatingHaploinsufficiency,
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.