The Arg653Gln mutation was studied and found not to affect the enzyme activity when present, but did seem to decrease the half-life and stability [R].
In test tubes, the A allele is only 38% as active as the G allele (P = 0.04) (R).
A study in Quebec showed an association in children with mutations in MTHFD1 having increased risk for heart defects, possibly in a folate status dependent manner (more so if their mother was not getting enough folate during pregnancy) [R].
Premenopausal women who were carriers of the G allele were more than 15 times as likely as non-carriers to develop signs of choline deficiency (P < 0.0001) on the low-choline diet (R).
A 2014 meta-analysis of nine studies totaling 4,302 cases of children born with neural tube defects concluded that white mothers carrying one or two "A" alleles were at 1.5 - 1.7x increased risk of having affected children compared to mothers with no "A" alleles (R).
Two reactions, mediated by methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase can convert 10-formyl tetrahydrofolate to 5,10-methylene tetrahydrofolate. While the formation of 5-methyl tetrahydrofolate is practically irreversible in vivo, the interconversion of 5,10-methylene tetrahydrofolate and 10-formyl tetrahydrofolate is closer to equilibrium. This means that 5,10-methylene tetrahydrofolate may be directed either toward homocysteine remethylation or away from it. The MTHFD1 G1958A polymorphism may thus affect the delicately balanced flux between 5,10-methylene tetrahydrofolate and 10-formyl tetrahydrofolate and thereby influence the availability of 5-methyl THF for homocysteine remethylation. This would increase demand for choline as a methyl-group donor. It is of interest that the risk of having a child with a neural tube defect increases in mothers with the A allele (R).