Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697092 | SCV000825683 | uncertain significance | Adams-Oliver syndrome 5 | 2018-08-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1450 of the NOTCH1 protein (p.Glu1450Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs147841035, ExAC 0.005%). 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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. |