ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.1420C>A (p.Arg474Ser) (rs866242631)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000371693 SCV000330155 pathogenic not provided 2016-01-15 criteria provided, single submitter clinical testing The R474S pathogenic variant in the KCNT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, missense variants at this same codon (R474H and R474C) have been reported in the Human Gene Mutation Database in association with KCNT1-related disorders (Stenson et al., 2014). The R474S variant was not observed in approximately 6500 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 R474S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We, therefore, interpret R474S as a pathogenic variant.

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.