Table 2.

MYBPC3 genetic mutations familial case studies presenting age-dependent penetrance

MYBPC3 mutation	No. of gene carriers	Age of probands during screening and their clinical presentation
c.2833_2834del, p.Arg945fs	4 of 176 HCM probands, 1 of 54 DCM probands, 1 relative of these 5 probands	61 ± 10 years (48–79 years); LV systolic dysfunction and suffer from cardiovascular events midlife and beyond[304]
c.2373dup, p.Trp792fs	27 of 49 probands; only 10 were symptomatic, 5 with borderline, and 12 asymptomatic	29–69 years; symptomatic HCM underscored by more advanced age of 54.7 ± 4.5 years; borderline HCM or unaffected carriers were 40 ± 14.0; non-gene carriers were 43 ± 12.9; asymptomatic at 37.8 ± 13.6[137]
c.2459G>A, p.Arg820Gln	8 probands (7 HCM, 1 DCM) of 250 HCM probands and 90 DCM probands. Among 24 relatives of these 8 probands, 17 were genotype-positive	16–77 years; burnout phase of HCM (patients with over dysfunction defined by an LVEF < 50%[11]) was described in those > 70 years of age The disease penetrance was 70% in subjects > 50 years of age by echocardiography and 100% by ECG, and in those aged < 50 years, it was 40% and 50%, respectively[305]
c.1777del, p.Ser593fs, (V592fs/8c)	15 of 94 probands, 24 relatives of these 15 probands were genotype-positive	48 ± 14 (16–83); 100% disease penetrance; in ≥ 50 years; 65% disease penetrance among individuals < 50 years[92]
g.47332282_47332306del	49 (13.8%) carried the 25-bp deletion (46 heterozygotes and three homozygotes) of 354 cases	48 ± 8 (Group 1 case) and 49 ± 12 (Group 2 case). Symptomatic carriers 55.7 ± 15.3 years; asymptomatic carriers 40 ± 14.1 years among 120 family members of 28 affected families with cardiomyopathy; 90% of the oldest members are symptomatic, whereas young and middle-aged are asymptomatic[90]
c.1000G>A, p.Glu334Lys	9 of 1017 unrelated probands were gene carriers	15–76 years; Delayed clinical presentation, reduced penetrance of HCM in women than men[306]
c.2308 + 1 G>A, pro108Alafs*9	13 probands and their relatives of a total of 107 individuals were screened; among the 54 gene carriers, 39 had HCM	Male-50.5 ± 15.9, female-65.5 ± 17.4 years; lower penetrance rate and later onset in women than men[307]