ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.851C>T (p.Pro284Leu) (rs376104770)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537829 SCV000659502 uncertain significance Adams-Oliver syndrome 5 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 284 of the NOTCH1 protein (p.Pro284Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs376104770, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in individuals affected with bicuspid aortic valve or left ventricular obstruction (PMID: 23578328, 28991257). ClinVar contains an entry for this variant (Variation ID: 477977). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000621230 SCV000739427 uncertain significance Cardiovascular phenotype 2017-05-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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