Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688022 | SCV000815618 | uncertain significance | Progressive myoclonic epilepsy | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 164 of the EPM2A protein (p.Ile164Val). This variant is present in population databases (rs199856913, gnomAD 0.006%). 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: 567836). 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 tolerated. 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 | RCV002317915 | SCV000849793 | uncertain significance | Inborn genetic diseases | 2017-05-31 | criteria provided, single submitter | clinical testing | The p.I164V variant (also known as c.490A>G), located in coding exon 3 of the EPM2A gene, results from an A to G substitution at nucleotide position 490. The isoleucine at codon 164 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species; however, valine is the reference amino acid in other 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. |
| Athena Diagnostics Inc | RCV000991960 | SCV001143865 | uncertain significance | not provided | 2018-12-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000991960 | SCV001782506 | uncertain significance | not provided | 2022-04-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |