ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3095A>G (p.His1032Arg)

gnomAD frequency: 0.00001  dbSNP: rs1397562033
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001055529 SCV001219927 uncertain significance Adams-Oliver syndrome 5 2019-04-11 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 1032 of the NOTCH1 protein (p.His1032Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001170151 SCV001332701 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2018-03-19 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001055529 SCV002553514 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002271176 SCV002553516 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV002298863 SCV002588074 uncertain significance not provided 2022-10-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV001170151 SCV002608283 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-11-09 criteria provided, single submitter clinical testing The p.H1032R variant (also known as c.3095A>G), located in coding exon 19 of the NOTCH1 gene, results from an A to G substitution at nucleotide position 3095. The histidine at codon 1032 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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.