ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5273A>G (p.Tyr1758Cys) (rs886039460)

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
GeneDx RCV000255765 SCV000322027 likely pathogenic not provided 2016-06-23 criteria provided, single submitter clinical testing The Y1769C variant that is likely pathogenic has not been published as a pathogenic variant, nor has it been reported as a benign variant 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 Y1769C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. This substitution alters a conserved position predicted to be within the transmembrane segment S6 of the fourth homologous domain of the SCN1A protein. A different missense variant at the same position (Y1769H) as well as missense variants in nearby residues (F1765L, I1771F/N, S1773F) have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Ambry Genetics RCV000624688 SCV000742333 uncertain significance Inborn genetic diseases 2017-08-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Ambry Genetics RCV000720726 SCV000851607 likely pathogenic History of neurodevelopmental disorder 2017-08-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,Rarity in general population databases (dbsnp, esp, 1000 genomes),Moderate segregation with disease (at least 3 informative meioses) for rare diseases.,Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family

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.