ClinVar Miner

Submissions for variant NM_000435.3(NOTCH3):c.245G>T (p.Cys82Phe) (rs1023306013)

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
Athena Diagnostics Inc RCV000516733 SCV000614257 pathogenic not provided 2015-12-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001097 SCV001158232 likely pathogenic none provided 2019-08-27 criteria provided, single submitter clinical testing The NOTCH3 c.245G>T; p.Cys82Phe variant (rs1023306013), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 447812). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The cysteine at codon 82 occurs within an EGF domain and is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. The vast majority of causative missense variants identified in individuals with CADASIL either create or remove EGF domain cysteine residues, as these are involved in the formation of disulfide bridges critical to protein folding (Dichgans 2000, Joutel 1997). Based on available information, this variant is considered to be likely pathogenic. References: Dichgans M et al. Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains. Eur J Hum Genet. 2000 Apr;8(4):280-5. Joutel A et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet. 1997 Nov 22;350(9090):1511-5.

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.