Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186749 | SCV000240316 | uncertain significance | not provided | 2018-03-06 | criteria provided, single submitter | clinical testing | p.Gly494Val (GGT>GTT): c.1481 G>T in exon 16 of the ALDH7A1 gene (NM_001182.4). The Gly494Val variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is highly conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a different missense mutation at the same position (Gly494Arg) and a missense mutation in the adjacent amino acid (Ala495Thr) have been previously reported in association with pyridoxine dependent epilepsy, supporting the functional importance of this region of the protein. However, the Gly494Val variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV001054885 | SCV001219243 | uncertain significance | Pyridoxine-dependent epilepsy | 2022-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 494 of the ALDH7A1 protein (p.Gly494Val). This variant is present in population databases (rs763418390, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ALDH7A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 204851). 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 ALDH7A1 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. |
Genome- |
RCV001054885 | SCV004050073 | uncertain significance | Pyridoxine-dependent epilepsy | 2023-04-11 | criteria provided, single submitter | clinical testing |