ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.5438G>T (p.Trp1813Leu) (rs755659037)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618087 SCV000739494 uncertain significance Cardiovascular phenotype 2019-09-12 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001202314 SCV001373422 uncertain significance Adams-Oliver syndrome 5 2019-09-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with leucine at codon 1813 of the NOTCH1 protein (p.Trp1813Leu). The tryptophan residue is highly conserved and there is a small physicochemical difference between tryptophan and leucine. This variant is present in population databases (rs755659037, ExAC 0.04%). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 520082). 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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