Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003558770 | SCV004292305 | likely pathogenic | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 141 of the MUT protein (p.Ala141Glu). This variant is present in population databases (rs565348836, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of MUT-related conditions (PMID: 28973083, 35361390). ClinVar contains an entry for this variant (Variation ID: 978683). 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. This variant disrupts the p.Ala141 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30209273; Invitae). 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. |
| Genetics and Prenatal Diagnosis Center, |
RCV001257407 | SCV001433963 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2020-01-01 | no assertion criteria provided | clinical testing |