In this study, we employed whole-exome sequencing to explore the possible causative gene for a family with overlap syndrome including CHD, conduction diseases and sudden cardiac death and identified a novel nonsense mutation in codon 1495 of SCN5A. The mutation locates in the highly conserved triad IFM motif (formed by residues 1485–1487)21 and is predicted to result in a premature protein truncation that is closely associated with channelopathies. This evidence concerns the gene SCN5A and channelopathy.