Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186728 | SCV000240295 | pathogenic | not provided | 2021-12-30 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on enzyme activity (Coulter-Mackie et al., 2012); This variant is associated with the following publications: (PMID: 19128417, 30043187, 32956737, 27342130, Ambegaonkar2017[abstract], 17068770, 24942048, 22784480) |
Invitae | RCV000796632 | SCV000936153 | pathogenic | Pyridoxine-dependent epilepsy | 2024-01-07 | 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 335 of the ALDH7A1 protein (p.Arg335Gln). This variant is present in population databases (rs754449549, gnomAD 0.007%). This missense change has been observed in individual(s) with pyridoxine-dependent epilepsy (PMID: 17068770; Invitae). 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.920G>A (p.Arg307Gln). ClinVar contains an entry for this variant (Variation ID: 204832). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ALDH7A1 function (PMID: 22784480). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV000186728 | SCV002497346 | likely pathogenic | not provided | 2022-01-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000796632 | SCV004048968 | likely pathogenic | Pyridoxine-dependent epilepsy | 2023-04-11 | criteria provided, single submitter | clinical testing |