ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4880G>A (p.Arg1627His)

gnomAD frequency: 0.00001  dbSNP: rs946083212
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460526 SCV000548949 likely benign Adams-Oliver syndrome 5 2023-10-18 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825645 SCV000967015 uncertain significance not specified 2017-08-29 criteria provided, single submitter clinical testing The p.Arg1627His (NM_017617.3 c.4880G>A) variant in NOTCH1 has not been previous ly reported in individuals with congenital heart disease. This variant has been identified in 1/12274 of East Asian chromosomes by the Genome Aggregation Databa se (gnomAD, http://gnomAD.broadinstitute.org; dbSNP rs946083212). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p .Arg1627 variant is uncertain.
Genome-Nilou Lab RCV000460526 SCV002553386 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270504 SCV002553387 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002339159 SCV002634984 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-09-24 criteria provided, single submitter clinical testing The p.R1627H variant (also known as c.4880G>A), located in coding exon 26 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 4880. The arginine at codon 1627 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in a newborn screening cohort (Ceyhan-Birsoy O et al. Am J Hum Genet, 2019 01;104:76-93). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.