ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4633A>G (p.Met1545Val)

dbSNP: rs796053150
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189164 SCV000242796 pathogenic not provided 2020-06-19 criteria provided, single submitter clinical testing This substitution is predicted to be within the transmembrane segment S1 of the fourth homologous domain; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28379373, 27876397, 27734276, 28817111, 30619928, 32090326, 32603808)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000189164 SCV001446648 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002517894 SCV003524740 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-11-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 207012). This missense change has been observed in individual(s) with clinical features of SCN2A-related conditions (PMID: 27734276, 28379373, 28817111). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1545 of the SCN2A protein (p.Met1545Val).

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