Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000555241 | SCV000629642 | uncertain significance | Werner syndrome | 2017-05-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with isoleucine at codon 721 of the WRN protein (p.Arg721Ile). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and isoleucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a WRN-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 C25"). 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. |