ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.1699A>G (p.Ile567Val) (rs369067940)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764819 SCV000895970 uncertain significance Aortic valve disorder; Adams-Oliver syndrome 5 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000826311 SCV000967894 likely benign not provided 2018-03-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000121657 SCV000085855 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000458785 SCV000548923 uncertain significance Adams-Oliver syndrome 5 2016-12-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 567 of the NOTCH1 protein (p.Ile567Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs369067940, ExAC 1.0%) but has not been reported in the literature in individuals with a NOTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 134907). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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.