Table 1. Results of genetic screening for MFN2 mutations in adult cardiomyopathy.
HCM, hypertrophic cardiomyopathy; DCM, dilated cardiomyopathy; MAF, minor allele frequency. MFN2 protein domains correspond to colored regions in Figure 1A.
| MFN2 variant | MFN2 domain | Polyphen 2 | ClinVar | HCM n = 286 | DCM1 n = 398 | DCM2 n = 281 probands (424 cases) | CM MAF n = 965 | gnomAD MAF n = 141,456 | MAF CM vs. gnomAD (p-value) | MAF CM vs. gnomAD (X2 stat) |
|---|---|---|---|---|---|---|---|---|---|---|
| S180R | GTPase | Benign | CMT2A | 1 het | Singleton | 1.591 E-05 | ||||
| V181M | GTPase | Prob dam | CMT2A | 1 family; 5 indiv | Singleton | 3.976 E-06 | ||||
| S263Y | GTPase | Pos dam | 1 het | Singleton | - | - | - | |||
| R274Q | GTPase | Benign | CMT2A | 1 family; 4 indiv | Singleton | 2.486 E-05 | ||||
| G298R | GTPase | Benign | CMT2A | 1 het | Singleton | 2.147 E-03 | ||||
| M393I | HR1 | Benign | Likely benign | 1 het | Singleton | 1.591 E-05 | ||||
| R400Q | HR1 | Prob dam | Uncertain significance | 2 hets | 1 het | 1.55 E-03 | 7.423 E-05 | <0.00001 | 89.595 | |
| Q413P | HR1 | Benign | 1 family; 1 indiv | Singleton | 1.193 E-05 | |||||
| R468H | inter | Pos dam | CMT2A | 1 het | 2 families; 5 indiv | 1.55 E-03 | 2.177 E-03 | NS | 0.3431 | |
| V705I | HR2 | Benign | Likely benign | 2 hets | 6 families; 15 indiv | 4.14 E-03 | 6.865 E-03 | NS | 2.0848 | |
| A716T | HR2 | Pos dam | CMT2A | 1 family; 1 indiv | Singleton | 1.308 E-04 |