ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5414T>C (p.Leu1805Pro) (rs201779159)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000594908 SCV000705654 uncertain significance not provided 2017-01-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620542 SCV000739441 uncertain significance Cardiovascular phenotype 2017-06-30 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000655262 SCV000777192 uncertain significance Adams-Oliver syndrome 5 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1805 of the NOTCH1 protein (p.Leu1805Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs201779159, ExAC 0.005%). This variant has been reported in an individual affected with bicuspid aortic valve (PMID: 28387797). ClinVar contains an entry for this variant (Variation ID: 499922). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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