ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2948T>G (p.Leu983Trp)

dbSNP: rs1553583560
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001207665 SCV001379028 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-04-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 983 of the SCN2A protein (p.Leu983Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 27290639). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 938446). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV003151834 SCV003840850 likely pathogenic not provided 2022-09-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This substitution is predicted to be within the transmembrane segment S6 of the second homologous domain; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27290639, 24077912)

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