ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3850T>C (p.Trp1284Arg) (rs796053001)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188932 SCV000242563 likely pathogenic not provided 2017-07-13 criteria provided, single submitter clinical testing p.Trp1284Arg (TGG>CGG): c.3850 T>C in exon 19 of the SCN1A gene (NM_001165963.1) The Trp1284Arg missense change has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution of an uncharged, non-polar Tryptophan residue with a positively charged Arginine residue. The variant alters a highly conserved position in the S3 subunit in the third transmembrane domain of the protein. A different amino acid substitution at this position (Trp1284Ser) has been published in association with Dravet syndrome. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, Trp1284Arg is a strong candidate for a pathogenic variant, although the possibility that it is a benign variant cannot be excluded.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV001375621 SCV001572543 likely pathogenic Severe myoclonic epilepsy in infancy 2021-04-25 criteria provided, single submitter clinical testing

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.