Table 2.
Previously described pathogenic or likely pathogenic variants in patients with cardiomyopathy
| DNA change (NM_001103.3) and zygosity | GnomAD v2.1.1 ALL frequency | GnomAD POPmax frequency | Varsome prediction and criteria | Supporting data | Phenotype | Reference |
|---|---|---|---|---|---|---|
| c.332G>T (p.Gly111Val) Het | 0.00005657 | NFE:0.0001084 | LP (PM2 strong, PP3 supp, PP5 supp, PS3 supp) | Functional data | HCM | Theis et al. (2006); Haywood et al. (2016) |
| c.355G>A (p.Ala119Thr) Het | NA | NA | P (PP5 very strong, PM2 strong, PP3 supp) | Segregates in multiple families | Variable symptoms including LVNC, DCM, and ventricular fibrillation often resulting in cardiac arrest | Bagnall et al. (2014); Chiu et al. (2010); Isbister et al. (2021); Kraoua et al. (2022) |
| c.668T>C (p.Leu223Pro) Het | NA | NA | VUS+ (PM2 strong, PP3 supp) | Segregates in a single family | LVNC | Park et al. (2021) |
| c.683T>C (p.Met228Thr) Het | NA | NA | VUS+ (PM2 strong, PP3 supp) | Segregates in a single family | Arrhythmia (paroxysmal supraventricular tachycardia/atrioventricular block) | Girolami et al. (2014) |
| c.740C>T (p.Thr247Met) Het | NA | NA | LP (PM2 strong, PP3 supp, PP3 moderate) | Segregates in a single family | Varying degrees and types of arrhythmias (supraventricular and ventricular); HCM observed in three patients | Prondzynski et al. (2019) |
| c.1418A>G (p.Tyr473Cys) Het | NA | NA | VUS+ (PM2 strong, PP3 supp) | Segregates in a single family member | Left dominant ACM observed in three patients | Good et al. (2020) |
| c.1883A>G (p.Glu628Gly) Het | NA | NA | VUS+ (PM2 strong, PP3 supp) | Segregates in a single family | Mild to moderate left ventricular hypertrophy | Burns et al. (2017); Chiu et al. (2010) |
| c.2578C>T (p.Gln860*) Hom | NA | NA | VUS+ (PM2 moderate, PVS1 moderate) | Functional data | Progressive heart failure symptoms, episodes of atrial fibrillation, and restrictive cardiomyopathy | Lindholm et al. (2021) |
| g.236898807_236903093del insTTCTTCAGCCAGTCCCATTGGCTCTTCTTCCAGAATACATC; c.698_1107delinsTTCTTCAGCCAGTCCCATTGGCTCTTCTTCCAGAATACATC (p.Asp233_Ser369delinsValLeuGlnProValProLeuAlaLeuLeuProGluTyrIle) Het | NA | NA | NA | Segregates in a single family + functional data | Varying degrees and types of arrhythmias (supraventricular and ventricular); LVNC in four patients; cardiac arrest in two cases | Lindholm et al. (2021) |
| chr1:236881685_236891006del; c.241+413_565del p.? Het | NA | NA | NA | Segregates in a single family | HCM observed in two patients, LVNC in a single patient | Singer et al. (2021) |
Abbreviations: ACM, arrhythmogenic cardiomyopathy; DCM, dilated cardiomyopathy; func, functional studies supporting pathogenicity; HCM, hypertrophic cardiomyopathy; het, heterozygous; hom, homozygous; LP, likely pathogenic; LVNC, left ventricular noncompaction cardiomyopathy; NA, not available; NFE, European (non‐Finnish); P, pathogenic; VUS, variant of uncertain significance; VUS+, VUS with minor pathogenic evidence; (a relative with DCM also carries the pathogenic variant OR a relative without phenotype does not carry the pathogenic variant).