Submissions for variant NM_001040142.2(SCN2A):c.1712G>A (p.Arg571His)

gnomAD frequency: 0.00013  dbSNP: rs138138150

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001721218	SCV000242849	uncertain significance	not provided	2021-06-25	criteria provided, single submitter	clinical testing	Reported in an individual with autism in the published literature (Guo H et al., 2018); 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; This substitution is predicted to be in the cytoplasmic loop between the first and second homologous domains; This variant is associated with the following publications: (PMID: 30564305, 24077912, 27535533)
Invitae	RCV000691494	SCV000819277	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2023-12-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 571 of the SCN2A protein (p.Arg571His). This variant is present in population databases (rs138138150, gnomAD 0.01%). This missense change has been observed in individual(s) with autism (PMID: 30564305). This variant is also known as g.166179706. ClinVar contains an entry for this variant (Variation ID: 207062). 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%. 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.
Fulgent Genetics, Fulgent Genetics	RCV000691494	SCV000895294	uncertain significance	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001721218	SCV002496529	uncertain significance	not provided	2022-01-01	criteria provided, single submitter	clinical testing
Channelopathy-Associated Epilepsy Research Center	RCV003483568	SCV004232417	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only