Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222378 | SCV000278564 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.P80S variant (also known as c.238C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 238. The proline at codon 80 is replaced by serine, an amino acid with similar properties. This amino acid position is 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. |
| Invitae | RCV000822283 | SCV000963078 | uncertain significance | Familial cancer of breast | 2023-05-17 | criteria provided, single submitter | clinical testing | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 234069). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is present in population databases (rs745355600, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 80 of the CHEK2 protein (p.Pro80Ser). |