*3.2. Genetic Analysis*

After excluding common polymorphisms on the basis of variant frequencies reported in gnomAD and HGVD and *in silico* analysis predictions, we identified 30 rare exonic (25 missense and 2 frameshift indel) and 3 splice site variants classified as pathogenic or likely pathogenic (Table 2) in 28 patients with LVNC and CHD. Eight variants were detected in *MYH7*, two in *TPM1*, and one in *ACTC1*, *ANK2*, *COL4A1*, *DAAM1*, *DSG2*, *DSP*, *FGF16*, *FGFR2*, *HCN4*, *JUP*, *MYBPC3*, *MYH6*, *MYL2*, *PKP2*, *PRDM16*, *RYR2*, and *TAZ* each. Sarcomere gene variants accounted for 50.0%. All variants affected conserved amino acid residues. In addition, the genetic collapsing test showed that variants in *MYH7* (*p* = 2.104 × 10<sup>−</sup>16, ranked first) and *TPM1* (*p* = 1.356 <sup>×</sup> 10<sup>−</sup>4, ranked second) reached significance (adjusted alpha = *p* < 2.74 <sup>×</sup> 10−4), which strongly suggested that variants in both genes increase the risk of LVNC (Table S4).


*J. Clin. Med.* **2020**, *9*, 785
