ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2738A>G (p.Lys913Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003221745 SCV003918754 uncertain significance not provided 2023-04-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the second homologous domain; Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV005227941 SCV005862726 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-08-28 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 913 of the SCN2A protein (p.Lys913Arg). This variant is present in population databases (rs367859080, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2499444). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SCN2A protein function with a positive predictive value of 95%. 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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