Submissions for variant NM_005670.4(EPM2A):c.818C>G (p.Ser273Cys)

dbSNP: rs796052436

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187409	SCV000240996	uncertain significance	not provided	2014-11-14	criteria provided, single submitter	clinical testing	p.Ser273Cys (TCC>TGC): c.818 C>G in exon 4 of the EPM2A gene (NM_005670.3). The S273C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S273C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a highly conserved position in the dual-specificity phophatase domain (DSPD) of the EPM2A protein (Singh et al., 2009), and a missense mutation in nearby residue (G279S) has been reported in association with epilepsy. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).