the Lys82Arg (exon 3) mutation was identified in the CALR3 gene. The proband (II:1) was aged 41 years at presentation and had severe exertional symptoms associated with left ventricular outflow tract obstruction. He has improved symptomatically following transseptal alcohol ablation. His 3 children are currently clinically normal but have decline genetic testing

the Arg73Gln (exon 3) mutation was identified in the proband (II:1), a 28-year-old male who had been diagnosed with FHC at age 18 years and on echocardiography was found to have severe asymmetric septal hypertrophy. He has a family history of FHC, but other family members have not been willing to participate in further evaluation. Previous genetic screening of sarcomere genes identified two missense mutations in myosin-binding protein C (MyBPC3; Asp745Gly and Pro873His)

For each patient, the summary of clinical and molecular data is tabulated in Supplementary Table 3. The synonymous variants identified for each patient are given in Supplementary Table 4.