ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.2206G>A (p.Gly736Arg)

gnomAD frequency: 0.00013  dbSNP: rs201662530
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
GeneDx RCV000498590 SCV000589957 uncertain significance not provided 2021-10-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar (ClinVar Variant ID# 432247; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660151 SCV000782145 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770643 SCV000902095 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-08-10 criteria provided, single submitter clinical testing
Invitae RCV001216676 SCV001388484 uncertain significance Adams-Oliver syndrome 5 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 736 of the NOTCH1 protein (p.Gly736Arg). This variant is present in population databases (rs201662530, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 432247). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV000770643 SCV002728217 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-11-11 criteria provided, single submitter clinical testing The p.G736R variant (also known as c.2206G>A), located in coding exon 13 of the NOTCH1 gene, results from a G to A substitution at nucleotide position 2206. The glycine at codon 736 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003419843 SCV004113479 uncertain significance NOTCH1-related condition 2023-02-08 criteria provided, single submitter clinical testing The NOTCH1 c.2206G>A variant is predicted to result in the amino acid substitution p.Gly736Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.030% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-139408963-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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.