ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5284C>T (p.Arg1762Trp)

gnomAD frequency: 0.00001  dbSNP: rs1356199208
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558986 SCV000659458 uncertain significance Adams-Oliver syndrome 5 2017-07-03 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NOTCH1-related disease. This sequence change replaces arginine with tryptophan at codon 1762 of the NOTCH1 protein (p.Arg1762Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.
GeneDx RCV001770496 SCV001993212 uncertain significance not provided 2023-02-16 criteria provided, single submitter clinical testing Has not been previously published in association with cardiac or connective tissue disease to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24277457)
Genome-Nilou Lab RCV000558986 SCV002553360 uncertain significance Adams-Oliver syndrome 5 2022-03-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002270701 SCV002553361 uncertain significance Aortic valve disease 1 2022-03-15 criteria provided, single submitter clinical testing

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