Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000465408 | SCV000548924 | uncertain significance | Adams-Oliver syndrome 5 | 2016-06-09 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NOTCH1-related disease. This sequence change replaces cysteine with arginine at codon 1040 of the NOTCH1 protein (p.Cys1040Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine. 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 C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |