ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.668G>A (p.Arg223Gln) (rs121917752)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000810006 SCV000950192 pathogenic Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 223 of the SCN2A protein (p.Arg223Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in affected individuals and to segregate with benign familial neonatal-infantile seizures in several families (PMID: 15048894, 29215089, 23360469). ClinVar contains an entry for this variant (Variation ID: 12879). Experimental studies have shown that this missense change causes neuronal hyperexcitability, boosting depolarizations in the subthreshold range and better sustaining neuronal spikes (PMID: 17021166). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013739 SCV000033986 pathogenic Benign familial neonatal-infantile seizures 2004-04-01 no assertion criteria provided literature only

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