ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.3062A>G (p.Tyr1021Cys) (rs1167405466)

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
Athena Diagnostics Inc RCV000518485 SCV000614273 pathogenic not provided 2018-06-22 criteria provided, single submitter clinical testing
GeneDx RCV000518485 SCV000779642 likely pathogenic not provided 2018-05-17 criteria provided, single submitter clinical testing The Y1021C variant in the NOTCH3 gene has been reported previously in individuals with clinical features of CADASIL (Kalimo et al., 2002; Piccirillo et al., 2008; Pantoni et al., 2010). The Y1021C variant is not observed in large population cohorts (Lek et al., 2016). The Y1021C 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. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, this variant introduces a new cysteine residue in the EGF-like 26 domain, a critical functional domain of the protein (Rutten et al., 2014). We interpret Y1021C as a likely 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.