ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6938G>A (p.Arg2313Gln) (rs371069660)

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
Invitae RCV000474849 SCV000548931 uncertain significance Adams-Oliver syndrome 5 2016-10-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2313 of the NOTCH1 protein (p.Arg2313Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs371069660, ExAC 0.02%) but 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it 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.
Ambry Genetics RCV000617779 SCV000739385 uncertain significance Cardiovascular phenotype 2017-07-19 criteria provided, single submitter clinical testing Insufficient evidence

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.