Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001910470 | SCV002191267 | likely pathogenic | Succinate-semialdehyde dehydrogenase deficiency | 2022-07-18 | 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 ALDH5A1 protein function. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 531 of the ALDH5A1 protein (p.Cys531Tyr). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with succinic semialdehyde dehydrogenase deficiency (PMID: 32395407, 32402538). ClinVar contains an entry for this variant (Variation ID: 1419591). Experimental studies have shown that this missense change affects ALDH5A1 function (PMID: 32395407, 32402538). 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. |
Elsea Laboratory, |
RCV001910470 | SCV002820049 | pathogenic | Succinate-semialdehyde dehydrogenase deficiency | 2021-03-08 | criteria provided, single submitter | curation |