ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.788C>T (p.Ala263Val) (rs387906686)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000118251 SCV000152618 pathogenic Benign familial neonatal-infantile seizures 2013-08-06 criteria provided, single submitter clinical testing
GeneDx RCV000189193 SCV000242825 pathogenic not provided 2017-06-05 criteria provided, single submitter clinical testing The A263V pathogenic variant in the SCN2A gene was initially reported as a de novo change in an individual with neonatal seizures and childhood-onset episodic ataxia, myoclonia, and pain (Liao et al., 2010). It was also reported as a de novo variant in monozygotic twins with Ohtahara syndrome (Touma et al., 2013). Functional analysis indicates A263V is a gain-of-function variant leading to neuronal hyperexcitability (Liao et al., 2010). This substitution alters a conserved position predicted to be in transmembrane segment S5 in the first homologous domain of the protein. A263V 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. Therefore, A263V is interpreted to be a pathogenic variant.
Neurogenetics Laboratory - MEYER,AOU Meyer RCV000416960 SCV000494503 pathogenic Epileptic encephalopathy 2016-11-16 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network,NIH RCV000625995 SCV000746601 pathogenic SCN2A-related condition 2017-11-12 criteria provided, single submitter clinical testing
Mendelics RCV000118251 SCV001135993 benign Benign familial neonatal-infantile seizures 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001035869 SCV001199208 pathogenic Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-08-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 263 of the SCN2A protein (p.Ala263Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in many individuals affected with SCN2A-related conditions (PMID: 20956790, 26645390, 27159988, 28065826). ClinVar contains an entry for this variant (Variation ID: 29888). This variant has been reported to affect SCN2A protein function (PMID: 20956790). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000189193 SCV001249545 pathogenic not provided 2018-12-01 criteria provided, single submitter clinical testing
OMIM RCV000022769 SCV000044058 pathogenic Episodic ataxia type 9 2013-05-01 no assertion criteria provided literature only
OMIM RCV001200935 SCV001371873 pathogenic Early infantile epileptic encephalopathy 11 2013-05-01 no assertion criteria provided literature only

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