Submissions for variant NM_001165963.4(SCN1A):c.4907G>A (p.Arg1636Gln)

dbSNP: rs121917995

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176634	SCV000228322	likely pathogenic	not provided	2015-03-13	criteria provided, single submitter	clinical testing
Invitae	RCV000463147	SCV000548769	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2023-08-04	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 68557). For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individual(s) with Lennox-Gastaut syndrome and seizures or early infantile epileptic encephalopathy (PMID: 17347258, 19589774, 26633542; Invitae). 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 1636 of the SCN1A protein (p.Arg1636Gln).
Ambry Genetics	RCV000623263	SCV000743065	likely pathogenic	Inborn genetic diseases	2017-10-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000176634	SCV001245865	pathogenic	not provided	2016-08-01	criteria provided, single submitter	clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV003448258	SCV004176443	pathogenic	Severe myoclonic epilepsy in infancy	2023-03-01	criteria provided, single submitter	clinical testing	The missense chr2:g.166848878C>T variant in SCN1A gene has been reported previously in heterozygous state in individual(s) affected with Early infantile epileptic encephalopathy (Retterer K et al., 2016). This variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Likely Pathogenic / Pathogenic (multiple submitters). The amino acid Arg at position 1636 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Arg1636Gln in SCN1A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The variant is predicted as damaging by SIFT. In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot	RCV000059431	SCV000090955	not provided	Macrocephaly and epileptic encephalopathy		no assertion provided	not provided
Center of Excellence for Medical Genomics, Chulalongkorn University	RCV002281560	SCV002570044	pathogenic	Migraine, familial hemiplegic, 3	2002-09-08	no assertion criteria provided	research