Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000427841 | SCV000536080 | uncertain significance | not provided | 2017-01-13 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the EPM2A gene. The G259E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G259E variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G259E 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000813908 | SCV000954290 | uncertain significance | Progressive myoclonic epilepsy | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 259 of the EPM2A protein (p.Gly259Glu). This variant is present in population databases (rs200641543, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EPM2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 392758). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
Ambry Genetics | RCV002411416 | SCV002674673 | uncertain significance | Inborn genetic diseases | 2019-04-14 | criteria provided, single submitter | clinical testing | The p.G259E variant (also known as c.776G>A), located in coding exon 4 of the EPM2A gene, results from a G to A substitution at nucleotide position 776. The glycine at codon 259 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |