Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186727 | SCV000240294 | pathogenic | not provided | 2020-09-18 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22784480, 26943461, 26224730, 20554659, 31302938, 32751059, 31589614) |
Revvity Omics, |
RCV001785493 | SCV002021339 | likely pathogenic | Pyridoxine-dependent epilepsy | 2019-01-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001785493 | SCV002211876 | uncertain significance | Pyridoxine-dependent epilepsy | 2022-05-16 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 203 of the ALDH7A1 protein (p.Trp203Gly). This variant is present in population databases (rs555896752, gnomAD 0.004%). This missense change has been observed in individual(s) with pyridoxine-dependent epilepsy (PMID: 20554659). This variant is also known as p.Trp175Gly. ClinVar contains an entry for this variant (Variation ID: 204831). 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. Experimental studies have shown that this missense change affects ALDH7A1 function (PMID: 22784480, 31302938). 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. |