ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.5839G>A (p.Glu1947Lys)

gnomAD frequency: 0.00001  dbSNP: rs1464068986
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001776679 SCV002013423 uncertain significance not provided 2019-12-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the C-terminal cytoplasmic domain
Labcorp Genetics (formerly Invitae), Labcorp RCV001885132 SCV002173076 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2021-01-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1947 of the SCN2A protein (p.Glu1947Lys). 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 not been reported in the literature in individuals with SCN2A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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