Table 6.

Variants in the MTHFD1 and MTHFD2 genes associated with congenital heart disease in humans.

Variant ID and Type	Population Allelic Frequency (GnomAD)	ACMG Classification	Associated CHD Phenotypes	References
MTHFD1
rs2236225 NM_005956.4: c.1958G>A NM_005956.4: p.Arg653Gln Missense	44%	Likely benign	VSD	[58]
			Conotruncal	[43]
			CHD in general	[43,59,60]
			TOF	[59]
			Aortic stenosis	[59]
rs2236222 NM_005956.4: c.2279+147A>G Non-coding transcript exon variant	9%	Benign	CHD in general	[58]
			VSD	[58]
rs11849530 NM_005956.4: c.2458-2060A>G Intron	21%	Benign	CHD in general	[58]
			VSD	[58]
rs11627387 NM_005956.4: c.2719-955G>A Non-coding transcript exon variant	28%	Benign	Conotruncal	[57]
MTHFD2
rs828858 NM_006636.4: c.-3575T>A Intron, Upstream	35%	Benign	CHD in general	[63]
			ASD	[63]
			VSD	[63]
			PDA	[63]

Congenital heart disease (CHD), ventricular septal defect (VSD), tetralogy of Fallot (TOF), atrial septal defects (ASD), and patent ductus arteriosus (PDA).