Figure 1

Family pedigree of the index patient. Family members diagnosed with HCM are shown with filled circles (females) or squares (males). Arrow indicates the index patient. The index patient's parents (I.1, I.2) died (d.) relatively young without known cardiac disease, and also three brothers of the index patient (II.1, II.2, II.3) have died of other causes without being known to have heart disease. A fourth brother (II.7) of the index patient has died of sudden death. A fifth brother (II.6) of the index patient has been diagnosed with moderate septal hypertrophy, but he could not be included in the genetic testing. In generations III and IV, two sons, four daughters and a granddaughter of the index patient were included in both the clinical evaluation and genetic testing. Massively parallel sequencing analysis of the index patient identified two rare MYBPC3 intronic variants (see Supplementary Fig. S1). Family genetic testing results (see Fig. 2) of these two intronic variants are shown for each family member analyzed. At the last clinical evaluation, the index patient’s daughter III.6 did not meet the criteria for HCM, and she was considered an unaffected carrier of the MYBPC3 c.3331−26T>G variant, according to further functional characterization of this intronic variant (see text). The age (years) of each family member is indicated, and also the age at diagnosis (Dx.) or last clinical evaluation (Ev.). N—unaffected, clinically evaluated.