Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001328517 | SCV001223698 | likely pathogenic | Hereditary hyperekplexia | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 175 of the GLRA1 protein (p.Met175Val). This variant is present in population databases (rs121918414, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive hyperekplexia (PMID: 11702206). 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 M147V (A830G). ClinVar contains an entry for this variant (Variation ID: 16068). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect GLRA1 function (PMID: 11702206). 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. |
| Revvity Omics, |
RCV000017446 | SCV003816905 | uncertain significance | Hyperekplexia 1 | 2023-02-24 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000017446 | SCV000037718 | pathogenic | Hyperekplexia 1 | 2001-09-01 | no assertion criteria provided | literature only |