Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700880 | SCV000829656 | uncertain significance | Adams-Oliver syndrome 5 | 2019-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 413 of the NOTCH1 protein (p.Val413Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs373770404, ExAC 0.02%). This variant has not been reported in the literature in individuals with NOTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 578001). 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: "Possibly Damaging"; 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769608 | SCV000901005 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2017-09-26 | criteria provided, single submitter | clinical testing |