ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.970C>A (p.His324Asn)

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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 RCV002651553 SCV003524801 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2023-10-30 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 324 of the SCN1A protein (p.His324Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 28012175; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 2203198). 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 not expected to disrupt SCN1A protein function with a negative predictive value of 95%. This variant disrupts the p.His324 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29142202). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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