Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001029829 | SCV001383132 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2019-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with serine at codon 93 of the MUT protein (p.Arg93Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed, in combination with another MUT variant, to segregate with methylmalonic aciduria in a family (Invitae). 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 disrupts the p.Arg93 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1670635, 16281286, 16490061, 7912889). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029829 | SCV001192613 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2019-08-13 | no assertion criteria provided | clinical testing |