Submissions for variant NM_001165963.4(SCN1A):c.2935G>A (p.Gly979Arg)

dbSNP: rs121918754

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000519810	SCV000617437	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing	The G979R pathogenic variant in the SCN1A gene has been previously reported in an individual with intractable childhood epilepsy with generlaized tonic-clonic seizures (ICEGTC) (Fujiwara et al., 2003). Functional studies have demonstrated that G979R leads to impaired channel function (Sugawara at al., 2003, Rhodes et al., 2005). The G979R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G979R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position predicted to be within the transmembrane segment S6 of the second homologous domain. Missense variants in nearby residues (M976I, V977M, V982L) have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, this variant is classified as pathogenic and it's presence is consistent with the diagnosis in this individual.
CeGaT Center for Human Genetics Tuebingen	RCV000519810	SCV002063918	pathogenic	not provided	2021-12-01	criteria provided, single submitter	clinical testing
UniProtKB/Swiss-Prot	RCV000059486	SCV000091011	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	not provided