Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001257307 | SCV003525174 | uncertain significance | Pyruvate dehydrogenase E1-beta deficiency | 2023-07-07 | criteria provided, single submitter | clinical testing | 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 978588). This missense change has been observed in individual(s) with pyruvate dehydrogenase lipoic acid synthetase deficiency (PDHLD) (PMID: 18164639). This variant is present in population databases (rs763842440, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 36 of the PDHB protein (p.Arg36Cys). |
OMIM | RCV001257307 | SCV001433853 | pathogenic | Pyruvate dehydrogenase E1-beta deficiency | 2021-08-06 | no assertion criteria provided | literature only |