ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.7209G>C (p.Gln2403His)

dbSNP: rs61751486
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769577 SCV000900974 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-02-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001305494 SCV001494831 uncertain significance Adams-Oliver syndrome 5 2024-06-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2403 of the NOTCH1 protein (p.Gln2403His). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 626572). 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 with a negative predictive value of 80%. 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.
GeneDx RCV001662808 SCV001874118 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; In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26582918)
Genome-Nilou Lab RCV002271021 SCV002553250 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001305494 SCV002555211 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing

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