ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2792G>C (p.Arg931Pro) (rs794726718)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180915 SCV000221891 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
Invitae RCV001376917 SCV001574112 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-10-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 931 of the SCN1A protein (p.Arg931Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of epileptic encephalopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 189961). 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 SCN1A protein function. This variant disrupts the p.Arg931 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22780858, 27231140, 28079314, 25243660, 12083760, 18076640, Invitae). 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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