Submissions for variant NM_005670.4(EPM2A):c.743C>T (p.Ala248Val)

gnomAD frequency: 0.00011  dbSNP: rs374043005

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000473835	SCV000552394	uncertain significance	Progressive myoclonic epilepsy	2022-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 248 of the EPM2A protein (p.Ala248Val). This variant is present in population databases (rs374043005, gnomAD 0.06%). 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: 411297). 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.
Athena Diagnostics Inc	RCV000518301	SCV000613260	uncertain significance	not specified	2016-11-10	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727516	SCV000709372	uncertain significance	not provided	2017-06-15	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000727516	SCV002542240	uncertain significance	not provided	2023-03-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000727516	SCV002575610	uncertain significance	not provided	2022-09-15	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002383827	SCV002672585	uncertain significance	Inborn genetic diseases	2017-11-02	criteria provided, single submitter	clinical testing	The p.A248V variant (also known as c.743C>T), located in coding exon 4 of the EPM2A gene, results from a C to T substitution at nucleotide position 743. The alanine at codon 248 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000781972	SCV000920427	uncertain significance	Seizure	2017-08-25	no assertion criteria provided	clinical testing