Submissions for variant NM_001040142.2(SCN2A):c.4712T>C (p.Ile1571Thr)

dbSNP: rs2105398463

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002545228	SCV003459839	pathogenic	Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11	2022-10-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SCN2A function (PMID: 32400968). 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: 1342682). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 30185235, 30776697, 32400968, 32613771). 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 isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1571 of the SCN2A protein (p.Ile1571Thr).
Neurology Department, Shenzhen Children's Hospital	RCV001847356	SCV002099478	pathogenic	West syndrome; Early infantile epileptic encephalopathy with suppression bursts	2022-02-16	no assertion criteria provided	clinical testing
Channelopathy-Associated Epilepsy Research Center	RCV002319728	SCV002605498	not provided	Complex neurodevelopmental disorder		no assertion provided	literature only