ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.769T>C (p.Cys257Arg) (rs794726771)

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
Center for Bioinformatics, Peking University RCV000180887 SCV000221856 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188845 SCV000242475 likely pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing p.Cys257Arg (TGT>CGT): c.769 T>C in exon 6 of the SCN1A gene (NM_001165963.1) The Cys257Arg missense change has not been published as a mutation, 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 the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as an uncharged Cysteine residue is replaced by a positively charged Arginine residue, and the loss of a Cysteine may affect disulfide bond formation in the protein. It alters a highly conserved position in the S5 segment of the first transmembrane domain of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. Therefore, based on the currently available information, Cys257Arg is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s).

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.