ClinVar Miner

Submissions for variant NM_005670.4(EPM2A):c.745G>T (p.Val249Leu)

dbSNP: rs1387516050
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556253 SCV000636479 pathogenic Progressive myoclonic epilepsy 2020-03-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. This variant has been observed in individual(s) with clinical features of Lafora disease (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 249 of the EPM2A protein (p.Val249Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine.
GeneDx RCV001563435 SCV001786380 uncertain significance not provided 2021-03-22 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33277415)

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