ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4495T>C (p.Phe1499Leu)

gnomAD frequency: 0.00001  dbSNP: rs121918632
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001090363 SCV001245870 pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001857344 SCV002245605 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2022-10-23 criteria provided, single submitter clinical testing This missense change has been observed in individuals with familial hemiplegic migraine (PMID: 19332696, 30498473). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1499 of the SCN1A protein (p.Phe1499Leu). ClinVar contains an entry for this variant (Variation ID: 12902). For these reasons, this variant has been classified as Pathogenic. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001090363 SCV002520019 pathogenic not provided 2021-10-07 criteria provided, single submitter clinical testing PP1_strong, PP3, PP4, PM1, PM2, PS3, PS4_moderate
OMIM RCV000013765 SCV000034012 pathogenic Migraine, familial hemiplegic, 3 2009-03-31 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000013765 SCV000091043 not provided Migraine, familial hemiplegic, 3 no assertion provided not provided
Channelopathy-Associated Epilepsy Research Center RCV003992154 SCV004809222 not provided Severe myoclonic epilepsy in infancy no assertion provided literature only

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.