ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.6481C>T (p.Pro2161Ser) (rs201518848)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727124 SCV000617310 uncertain significance not provided 2020-09-24 criteria provided, single submitter clinical testing Reported in an individual with bicuspid aortic valve (Bonachea et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#449324; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 25260786)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727124 SCV000705953 uncertain significance not provided 2017-03-17 criteria provided, single submitter clinical testing
Invitae RCV001058437 SCV001223010 uncertain significance Adams-Oliver syndrome 5 2020-07-03 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 2161 of the NOTCH1 protein (p.Pro2161Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs201518848, ExAC 0.01%). This variant has been observed in an individual with bicuspid aortic valve (PMID: 25260786). ClinVar contains an entry for this variant (Variation ID: 449324). 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 C). 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. 5
Baylor Genetics RCV001335846 SCV001529089 uncertain significance Aortic valve disease 1 2018-04-20 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GenomeConnect - Invitae Patient Insights Network RCV001535474 SCV001749401 not provided Adams-Oliver syndrome 5; Aortic valve disorder no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 12-27-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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