ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4783C>A (p.Leu1595Ile)

gnomAD frequency: 0.00002  dbSNP: rs756238700
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 RCV000689911 SCV000817581 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1595 of the SCN1A protein (p.Leu1595Ile). This variant is present in population databases (rs756238700, gnomAD 0.002%). This missense change has been observed in individuals with clinical features of autosomal dominant SCN1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 569312). 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 with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV002263933 SCV002544106 uncertain significance not provided 2022-06-01 criteria provided, single submitter clinical testing SCN1A: PP2
GeneDx RCV002263933 SCV003195062 uncertain significance not provided 2023-01-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the intracellular loop between the S2 and S3 transmembrane segments of the fourth homologous domain

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.