Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000692232 | SCV000820044 | uncertain significance | Familial cancer of breast | 2018-04-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with alanine at codon 505 of the CHEK2 protein (p.Ser505Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHEK2-related disease. Experimental studies suggest that this missense change does not impact CHEK2 protein function (PMID: 12855706). 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 | RCV003352987 | SCV004055675 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-11 | criteria provided, single submitter | clinical testing | The p.S505A variant (also known as c.1513T>G), located in coding exon 13 of the CHEK2 gene, results from a T to G substitution at nucleotide position 1513. The serine at codon 505 is replaced by alanine, an amino acid with similar 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. |