ClinVar Miner

Submissions for variant NM_017617.5(NOTCH1):c.4451A>G (p.Asn1484Ser) (rs759828439)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770628 SCV000902079 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-04-24 criteria provided, single submitter clinical testing
Invitae RCV000805083 SCV000945026 uncertain significance Adams-Oliver syndrome 5 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1484 of the NOTCH1 protein (p.Asn1484Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs759828439, ExAC 0.02%). This variant has not been reported in the literature in individuals with NOTCH1-related disease. 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 C45"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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