Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Soonchunhyang University Bucheon Hospital, |
RCV000490459 | SCV000267345 | likely pathogenic | Hyperekplexia 1 | 2016-03-18 | criteria provided, single submitter | reference population | |
| Invitae | RCV001853386 | SCV002250237 | likely pathogenic | Hereditary hyperekplexia | 2022-04-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 225379). 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. This variant disrupts the p.Arg93 amino acid residue in GLRA1. Other variant(s) that disrupt this residue have been observed in individuals with GLRA1-related conditions (PMID: 20631190), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects GLRA1 function (PMID: 20631190, 24108130). 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 GLRA1 protein function. This variant is also known as R65W. This missense change has been observed in individuals with autosomal recessive hyperekplexia (PMID: 20631190, 24108130). This variant is present in population databases (rs199547699, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 93 of the GLRA1 protein (p.Arg93Trp). |