ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3631G>A (p.Glu1211Lys) (rs387906684)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000118248 SCV000152615 pathogenic Benign familial neonatal-infantile seizures 2013-05-15 criteria provided, single submitter clinical testing
GeneDx RCV000189138 SCV000242770 pathogenic not provided 2017-09-20 criteria provided, single submitter clinical testing p.Glu1211Lys (GAA>AAA): c.3631 G>A in exon 19 of the SCN2A gene (NM_021007.2). The E1211K missense mutation in the SCN2A gene has been published as a de novo mutation in a patient with infantile spasms which progressed to severe generalized epilepsy. Functional studies suggested that the E1211K variant alters the channel activity of the SCN2A protein (Ogiwara et al., 2009). The E1211K variant 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 E1211K 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 transmembrane segment S1 in the third homologous domain of the SCN2A protein. The E1211K variant is considered a pathogenic mutation. The variant is found in INFANT-EPI panel(s).
UCLA Clinical Genomics Center, UCLA RCV000022767 SCV000255458 likely pathogenic Early infantile epileptic encephalopathy 11 2013-07-16 criteria provided, single submitter clinical testing
Invitae RCV000806278 SCV000946267 pathogenic Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1211 of the SCN2A protein (p.Glu1211Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of early infantile epileptic encephalopathy (PMID: 19786696, 25326637, 28379373, 25459969). In several of these individuals this variant was observed to be de novo (PMID: 19786696, 25326637). ClinVar contains an entry for this variant (Variation ID: 29886). Experimental studies have shown that this missense change significantly changed the functional property of the sodium channels leading to both augmented and reduced channel activities by electrophysiological analyses in the cells (PMID: 19786696). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000022767 SCV000044056 pathogenic Early infantile epileptic encephalopathy 11 2009-09-29 no assertion criteria provided literature only

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