Table 7.
Variants in the MTHFR gene associated with congenital heart disease in humans.
| Variant ID and Type | Population Allelic Frequency (GnomAD) | ACMG Classification | Associated CHD Phenotypes | References |
|---|---|---|---|---|
| rs1801133 NM_005957.5: c. 665C>T * NM_005957.5: p. Ala222Val Missense |
31% | Benign | CHD in general | [64,65,66] |
| VSD | [69] | |||
| PDA | [70] | |||
| Conotruncal | [42] | |||
| TOF | [61,71] | |||
| PVS | [72,73] | |||
| HLHS | [72] | |||
| CoA | [72,74] | |||
| AVS | [72] | |||
| PA+IVS | [73] | |||
| ASD | [70] | |||
| rs1801131 NM_005957.5: c.1286A>C ** NM_005957.5: p.Glu429Ala Missense |
29% | Variant of uncertain significance | CHD in general | [64] |
| PDA | [75] | |||
| Conotruncal | [76,77,78] | |||
| rs2066470 NM_005957.5: c.117C>T NM_005957.5: p.Pro39= Silent |
10% | Benign | CHD in general | [68] |
Congenital heart disease (CHD), ventricular septal defect (VSD), tetralogy of Fallot (TOF), atrial septal defects (ASD), patent ductus arteriosus (PDA), pulmonary valve stenosis (PVS), hypoplastic left heart syndrome (HLHS), coarctation of the aorta (CoA), aortic valve stenosis (AVS), pulmonary atresia with intact ventricular septum (PA+IVS). * Historically c.677C>T. ** Historically c. 1298A>C.