Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669525 | SCV000794285 | uncertain significance | Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency | 2017-10-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001376545 | SCV001386442 | pathogenic | not provided | 2023-08-04 | 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: 553978). This missense change has been observed in individual(s) with methylmalonic acidemia (PMID: 16281286; Invitae). 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 serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 306 of the MUT protein (p.Ser306Phe). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526004 | SCV005039378 | uncertain significance | not specified | 2024-03-29 | criteria provided, single submitter | clinical testing | Variant summary: MMUT c.917C>T (p.Ser306Phe) results in a non-conservative amino acid change located in the methylmalonyl-CoA mutase, alpha chain, catalytic domain (IPR006098) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250844 control chromosomes. c.917C>T has been reported in the literature in at least one homozygous individual affected with f Methylmalonic Acidemia and at least one individual from a cohort with diagnosed inborn errors of metabolism (e.g., Worgan_2006, Adhikari_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32778825, 16281286). ClinVar contains an entry for this variant (Variation ID: 553978). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |