ClinVar Miner

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

dbSNP: rs121917986
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Total submissions: 6
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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

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