Submissions for variant NM_001165963.4(SCN1A):c.4168G>A (p.Val1390Met)

dbSNP: rs121917986

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Bioinformatics, Peking University	RCV000059411	SCV000221778	pathogenic	Severe myoclonic epilepsy in infancy	2014-12-20	criteria provided, single submitter	research
GeneDx	RCV000254970	SCV000322269	pathogenic	not provided	2021-11-15	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the third homologous domain; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20431604, 26096185, 31864146, 12083760, 17347258, 15277629, 22780858, 31879226, 29141279, 33108073, 23762420, 31031587, 18804930)
Invitae	RCV000804975	SCV000944916	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2021-09-04	criteria provided, single submitter	clinical testing	This sequence change replaces valine with methionine at codon 1390 of the SCN1A protein (p.Val1390Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Dravet syndrome (PMID: 12083760, 20431604, 22780858, 23762420, 29141279, 30182498). In at least one individual the variant was observed to be de novo. This variant is also known as c.A3169G p.V1380M. ClinVar contains an entry for this variant (Variation ID: 68537). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot	RCV000059411	SCV000090935	not provided	Severe myoclonic epilepsy in infancy		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000254970	SCV001740812	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000254970	SCV001931131	pathogenic	not provided		no assertion criteria provided	clinical testing