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

dbSNP: rs797045942

Total submissions: 4

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)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001390104	SCV001591726	pathogenic	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2024-05-02	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 856 of the SCN2A protein (p.Arg856Gln). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 212125). 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 with a positive predictive value of 95%. 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. For these reasons, this variant has been classified as Pathogenic.
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.