Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001186517 | SCV001352969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-11 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001186517 | SCV002711514 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-21 | criteria provided, single submitter | clinical testing | The p.L355P variant (also known as c.1064T>C), located in coding exon 9 of the CHEK2 gene, results from a T to C substitution at nucleotide position 1064. The leucine at codon 355 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003607411 | SCV004521569 | uncertain significance | Familial cancer of breast | 2023-08-11 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 355 of the CHEK2 protein (p.Leu355Pro). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. 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: 924878). |