Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001227875 | SCV001400253 | uncertain significance | Familial cancer of breast | 2019-09-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CHEK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 353 of the CHEK2 protein (p.Val353Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |