ClinVar

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg108 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16281286, 24464670, 27578510, 11528502). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with methylmalonic aciduria (PMID: 16281286, 23430940). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 108 of the MUT protein (p.Arg108Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.