ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.3569A>G (p.His1190Arg)

gnomAD frequency: 0.00001  dbSNP: rs775438678
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697399 SCV000826007 uncertain significance Adams-Oliver syndrome 5 2023-05-21 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NOTCH1 protein function. ClinVar contains an entry for this variant (Variation ID: 575237). This variant has not been reported in the literature in individuals affected with NOTCH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1190 of the NOTCH1 protein (p.His1190Arg).
GeneDx RCV001557790 SCV001779617 uncertain significance not provided 2022-07-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function
Genome-Nilou Lab RCV000697399 SCV002553485 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270969 SCV002553486 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002485700 SCV002794307 uncertain significance Aortic valve disease 1; Adams-Oliver syndrome 5 2021-08-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV003163215 SCV003861526 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-12-31 criteria provided, single submitter clinical testing The p.H1190R variant (also known as c.3569A>G), located in coding exon 22 of the NOTCH1 gene, results from an A to G substitution at nucleotide position 3569. The histidine at codon 1190 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.
CeGaT Center for Human Genetics Tuebingen RCV001557790 SCV004184852 uncertain significance not provided 2023-11-01 criteria provided, single submitter clinical testing NOTCH1: PM2, BP4

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