ClinVar Miner

Submissions for variant NM_005670.4(EPM2A):c.743C>T (p.Ala248Val) (rs374043005)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473835 SCV000552394 uncertain significance Progressive myoclonic epilepsy 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 248 of the EPM2A protein (p.Ala248Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs374043005, ExAC 0.08%). This variant has not been reported in the literature in individuals with EPM2A-related disease. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727516 SCV000709372 uncertain significance not provided 2017-06-15 criteria provided, single submitter clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000781972 SCV000920427 uncertain significance Seizures 2017-08-25 no assertion criteria provided clinical testing

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