ClinVar Miner

Submissions for variant NM_005670.4(EPM2A):c.524A>G (p.His175Arg) (rs1264840627)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768207 SCV000898671 uncertain significance Lafora disease 2018-11-28 criteria provided, single submitter clinical testing EPM2A NM_005670.3 exon 3 p.His175Arg (c.524A>G): This variant has not been reported in the literature but is present in 0.006% (1/15304) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/6-145956575-T-C). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV001205326 SCV001376575 uncertain significance Progressive myoclonic epilepsy 2019-07-19 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 175 of the EPM2A protein (p.His175Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with EPM2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 626099). 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. 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.

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