ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.319C>T (p.Arg107Trp)

gnomAD frequency: 0.00002  dbSNP: rs768965053
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
GeneDx RCV001756744 SCV001987691 uncertain significance not provided 2019-05-31 criteria provided, single submitter clinical testing Reported in two patients with leukoencephalopathy; however further clinical and familial segregation information were not provided (Ungaro et al., 2009); Reported in a patient with history of a lacunar stroke and hypertension; however, information about parental testing was not provided and functional characterization of the variant was not performed (Kilarski et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26305465, 19006080)
Athena Diagnostics RCV001756744 SCV004229494 uncertain significance not provided 2023-07-05 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function. Greater than 90% of NOTCH3 pathogenic variants associated with CADASIL involve the gain or loss of a cysteine residue within the epidermal growth factor (EGF)-like repeat domain (PMID: 32457593, 20301673).

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.