ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.157G>A (p.Val53Met) (rs757497167)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477441 SCV000548934 uncertain significance Adams-Oliver syndrome 5 2018-06-13 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 53 of the NOTCH1 protein (p.Val53Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs757497167, ExAC 0.03%). This variant has been reported in an individual affected with bicuspid aortic valve and thoracic aortic aneurysm, as well as their affected father (PMID: 25907466). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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