ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4971C>G (p.Ser1657Arg) (rs367838230)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476688 SCV000548937 uncertain significance Adams-Oliver syndrome 5 2018-02-27 criteria provided, single submitter clinical testing This sequence change replaces serine with arginine at codon 1657 of the NOTCH1 protein (p.Ser1657Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. While this variant is present in population databases (rs367838230), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant was reported in an individual affected with bicuspid aortic valve (BAV) (PMID: 26820064). ClinVar contains an entry for this variant (Variation ID: 180459). 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. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Blueprint Genetics RCV000157395 SCV000207133 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2013-12-13 no assertion criteria provided clinical testing

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