ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2567G>A (p.Arg856Gln)

dbSNP: rs797045942
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193985 SCV000248809 likely pathogenic Seizure 2014-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000413708 SCV000490917 pathogenic not provided 2021-11-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32090326, 27781031, 28379373, 30859550, 31558572)
Invitae RCV001390104 SCV001591726 pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-10-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg856 amino acid residue in SCN2A. Other variant(s) that disrupt this residue have been observed in individuals with SCN2A-related conditions (PMID: 26291284), which suggests that this may be a clinically significant amino acid residue. 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: 212125). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 27781031, 30859550). 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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 856 of the SCN2A protein (p.Arg856Gln).
GenomeConnect - Simons Searchlight RCV001265401 SCV001443527 pathogenic Complex neurodevelopmental disorder 2017-12-15 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-12-15 and interpreted as Pathogenic. Variant was initially reported on 2017-09-27 by GTR ID of laboratory name Laboratorio di Diagnosis Citogenetica Prenatal e Molecolare . The reporting laboratory might also submit to ClinVar.

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