Table 8.

Variants in the MTR and MTRR genes associated with congenital heart disease in humans.

Variant ID and Type	Population Allelic Frequency (GnomAD)	ACMG Classification	Associated CHD Phenotypes	References
	MTR
rs1805087 NM_000254.3: c.2756A>G NM_000254.3: p.Asp919Gly Missense	20%	Variant of uncertain significance	CHD in general	[58]
rs1770449 NM_000254.3: c.2594+15T>C Intron	32%	Benign	CHD in general	[80]
			Septal	[80]
			Conotruncal	[80]
rs1050993 NM_000254.3: c.*1361A>G 3 prime UTR variant	73%	Benign	CHD in general	[80]
			Septal	[80]
			Conotruncal	[80]
rs2275565 NM_000254.3: c.2775+157G>T Intron	28%	Benign	CHD in general	[63]
rs28372871 NM_000254.3: c.-472G>T Promoter, regulatory variant	47%	Benign	CHD in general	[81]
rs1131450 NM_000254.3: c.*905G>A 3 prime UTR variant	28%	Benign	CHD in general	[81]
	MTRR
rs1801394 NM_002454.3: c.66A>G NM_002454.3: p.Ile22Met Missense	47%	Variant of uncertain significance	CHD in general	[79,82,83,84,85,86]
			Conotruncal	[43]
			TOF	[44,85]
			Acyanotic	[87]
			ASD	[86]
			VSD	[44,86,88,89]
			PDA	[86]
rs1532268 NM_002454.3: c.524C>T NM_002454.3: p.Ser175Leu Missense	31%	Benign	CHD in general	[83,86]
			Acyanotic	[87]
			ASD	[86]
			VSD	[86,88,89,90]
rs326119 NM_002454.3: c.-26+755C>A Intron	56%	Benign	CHD in general, conotruncal CHD, septation defects, LVOTO, RVOTO, ASD, VSD, TOF	[91]

Congenital heart disease (CHD), ventricular septal defect (VSD), tetralogy of Fallot (TOF), atrial septal defects (ASD), patent ductus arteriosus (PDA), left ventricular outflow tract obstruction (LVOTO), right ventricular outflow tract obstruction (RVOTO), the asterisk (*) at rs1050993 and rs1131450 indicates that the mutations are located in the 3 prime UTR region.