ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4633A>G (p.Ile1545Val) (rs121917975)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001069069 SCV001234214 pathogenic Early infantile epileptic encephalopathy 2019-02-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 1545 of the SCN1A protein (p.Ile1545Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with SCN1A-related conditions, including several de novo observations (PMID: 17347258, 28202706, 30619928). ClinVar contains an entry for this variant (Variation ID: 68551). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Institute for Genomic Medicine (IGM) Clinical Laboratory,Nationwide Children's Hospital RCV001249684 SCV001423679 pathogenic Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-11-30 criteria provided, single submitter clinical testing [ACMG/AMP: PS2, PM1, PM2, PP2, PP3] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is located in a mutational hotspot and/or critical and well-established functional domain [PM1], is absent from or rarely observed in large-scale population databases [PM2], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3].
UniProtKB/Swiss-Prot RCV000059425 SCV000090949 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.