ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4024G>A (p.Gly1342Ser) (rs748933222)

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 RCV000245893 SCV000319628 uncertain significance Cardiovascular phenotype 2015-04-09 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000999290 SCV001155855 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV001058313 SCV001222873 uncertain significance Adams-Oliver syndrome 5 2019-03-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1342 of the NOTCH1 protein (p.Gly1342Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs748933222, ExAC 0.003%). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 264014). 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. 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.