Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493956 | SCV000582192 | likely pathogenic | not provided | 2015-10-27 | criteria provided, single submitter | clinical testing | The G47R variant in the GLRA1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G47R variant 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. The G47R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The G47R variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded |
Invitae | RCV001865543 | SCV002283352 | uncertain significance | Hereditary hyperekplexia | 2022-08-22 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 429587). This variant has not been reported in the literature in individuals affected with GLRA1-related conditions. This variant is present in population databases (rs759998394, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 47 of the GLRA1 protein (p.Gly47Arg). |