ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4468A>G (p.Met1490Val) (rs869312663)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209898 SCV000265510 pathogenic Early infantile epileptic encephalopathy 11 2004-04-10 criteria provided, single submitter research
Invitae RCV000640635 SCV000762229 likely pathogenic Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2018-02-10 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 1490 of the SCN2A protein (p.Met1490Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with with moderate intellectual disability, speech delay and seizures (PMID: 28554332). It has been observed to be de novo in an individual with early onset seizures and movement disorder (Invitae). ClinVar contains an entry for this variant (Variation ID: 224077). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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