Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV001542450 | SCV001761157 | uncertain significance | Methylcobalamin deficiency type cblG | 2020-07-01 | criteria provided, single submitter | clinical testing | The c.2249T>C,p.Phe750Ser missense variant identified in the MTR gene has not beenreported in the literature. This variant is not reported in gnomAD database, indicating this is a rare allele. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. This substitutionis a part of B12-binding N-terminal domain, and in methionine synthase the cobalamin cofactor is sandwiched between the B12-binding domain and an ~90 residues N-terminal domain forming a helical bundle comprising two pairs of antiparallel helices [PMID: 27153729]. Based on the available evidence, the variant c.2249T>C,p.Phe750Ser in the MTRgene is classified as a Variant of Uncertain Significance. |