Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000012752 | SCV004193954 | likely pathogenic | Pyruvate dehydrogenase E3 deficiency | 2023-10-05 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000012752 | SCV004295525 | likely pathogenic | Pyruvate dehydrogenase E3 deficiency | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 361 of the DLD protein (p.Met361Val). This variant is present in population databases (rs121964993, gnomAD 0.002%). This missense change has been observed in individual(s) with with dihydrolipoamide dehydrogenase deficiency (PMID: 11687750). 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: 11972). 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 DLD protein function with a positive predictive value of 80%. 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. |
| OMIM | RCV000012752 | SCV000032987 | pathogenic | Pyruvate dehydrogenase E3 deficiency | 2001-11-01 | no assertion criteria provided | literature only |