ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4988G>A (p.Arg1663Gln) (rs749490844)

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
Ambry Genetics RCV000620626 SCV000739404 uncertain significance Cardiovascular phenotype 2016-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000766056 SCV000897512 uncertain significance Aortic valve disorder; Adams-Oliver syndrome 5 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000557460 SCV000659452 uncertain significance Adams-Oliver syndrome 5 2017-01-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1663 of the NOTCH1 protein (p.Arg1663Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. While this variant is present in population databases (rs749490844), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a NOTCH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but 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.