Submissions for variant NM_001040142.2(SCN2A):c.1820G>A (p.Arg607Gln)

dbSNP: rs755003900

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000626121	SCV000746748	likely benign	not specified	2020-05-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001549293	SCV001769417	likely pathogenic	not provided	2020-01-11	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); This substitution is predicted to be in the cytoplasmic loop between the first and second homologous domains; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV002529776	SCV003504506	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2023-08-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 607 of the SCN2A protein (p.Arg607Gln). 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. ClinVar contains an entry for this variant (Variation ID: 522924). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003985403	SCV004107268	uncertain significance	SCN2A-related disorder	2023-01-26	criteria provided, single submitter	clinical testing	The SCN2A c.1820G>A variant is predicted to result in the amino acid substitution p.Arg607Gln. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.