Submissions for variant NM_001165963.4(SCN1A):c.4973C>T (p.Thr1658Met)

dbSNP: rs121917922

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Bioinformatics, Peking University	RCV000059523	SCV000221965	pathogenic	Severe myoclonic epilepsy in infancy	2014-12-20	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000529623	SCV000633868	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2022-01-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Thr1658 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 17561957; Invitae), 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 SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 68643). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 18930999, 20522430). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1658 of the SCN1A protein (p.Thr1658Met).
NeuroMeGen, Hospital Clinico Santiago de Compostela	RCV000059523	SCV000693792	likely pathogenic	Severe myoclonic epilepsy in infancy	2018-01-01	criteria provided, single submitter	clinical testing
UniProtKB/Swiss-Prot	RCV000059523	SCV000091054	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	not provided