Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668074 | SCV000792619 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-07-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001855493 | SCV002274309 | pathogenic | not provided | 2023-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 328 of the MUT protein (p.Leu328Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with methylmalonic (PMID: 15781192, 22614770, 26790480, 32754920). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 552752). 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 with a positive predictive value of 95%. This variant disrupts the p.Leu328 amino acid residue in MUT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15643616, 17113806, 25125334, 27167370). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000668074 | SCV002517626 | pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000668074 | SCV002785459 | likely pathogenic | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2021-07-16 | criteria provided, single submitter | clinical testing |