Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
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. |