Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000533182 | SCV000633204 | uncertain significance | Familial cancer of breast | 2017-05-23 | criteria provided, single submitter | clinical testing | In summary, this variant has uncertain impact on CHEK2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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"). This variant has not been reported in the literature in individuals with a CHEK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with isoleucine at codon 217 of the CHEK2 protein (p.Arg217Ile). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and isoleucine. |
Color Diagnostics, |
RCV003584653 | SCV004361390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with isoleucine at codon 217 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CHEK2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |