Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000635808 | SCV000757231 | uncertain significance | Familial cancer of breast | 2022-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 318 of the CHEK2 protein (p.Arg318Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 530137). 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: "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. |
Ambry Genetics | RCV002377378 | SCV002690730 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-29 | criteria provided, single submitter | clinical testing | The p.R318P variant (also known as c.953G>C), located in coding exon 8 of the CHEK2 gene, results from a G to C substitution at nucleotide position 953. The arginine at codon 318 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |