Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489116 | SCV000577814 | likely pathogenic | not provided | 2015-04-29 | criteria provided, single submitter | clinical testing | The R326G variant has not been published as a pathogenic variants, nor has it been reported as a benign polymorphism to our knowledge. The R326G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (Y316C, A324T, L328F, L328P) have been reported in the Human Gene Mutation Database in association with methylmalonic aciduria (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
| Invitae | RCV000489116 | SCV002232453 | pathogenic | not provided | 2023-05-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MUT protein function. ClinVar contains an entry for this variant (Variation ID: 427176). This missense change has been observed in individual(s) with methylmalonic acidemia (PMID: 29158924, 30022420, 30712249). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 326 of the MUT protein (p.Arg326Gly). |