*2.5. Variant Screening*

After obtaining informed consent from the patients or their parents, DNA was isolated from a whole-blood or heart tissue sample from each patient. Next-generation sequencing (NGS) was performed with 182 cardiac disorder-related genes (Table S1) using the Ion PGM System (Life Technologies, Carlsbad, CA, USA).

After all candidate pathogenic variants passed the selection criteria, to validate the result of NGS, Sanger sequencing was conducted.

## *2.6. Data Analysis and Variant Classification*

The gnomAD database and Human Genetic Variation Database (HGVD), which contain data from 1208 Japanese individuals, was used to determine the allelic frequency of all detected variants. All variants were filtered with a minor allele frequency (MAF) of ≥0.0005 among the gnomAD and HGVD population. To evaluate the pathogenicity of the variants, seven different *in silico* predictive algorithms were used (Table S2). The pathogenicity of an identified variant was evaluated by the guidelines of the American College of Medical Genetics and Genomics [15].
