ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.5408A>T (p.Glu1803Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003808490 SCV004592491 likely pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2023-02-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1803 of the SCN2A protein (p.Glu1803Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. 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. This variant disrupts the p.Glu1803 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30552426). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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