Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001257314 | SCV003525335 | likely pathogenic | Pyruvate dehydrogenase E1-beta deficiency | 2023-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 105 of the PDHB protein (p.Arg105Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of pyruvate dehydrogenase complex deficiency (PMID: 19924563). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.313G>A. ClinVar contains an entry for this variant (Variation ID: 978595). 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 PDHB protein function. 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 | RCV001257314 | SCV001433860 | pathogenic | Pyruvate dehydrogenase E1-beta deficiency | 2020-09-28 | no assertion criteria provided | literature only |