Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000701628 | SCV000830439 | uncertain significance | Werner syndrome | 2019-10-24 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs759390217, ExAC 0.01%). This sequence change replaces threonine with lysine at codon 1345 of the WRN protein (p.Thr1345Lys). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and lysine. This variant has not been reported in the literature in individuals with 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: "Tolerated"; 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. |