Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001045771 | SCV001209642 | uncertain significance | Familial cancer of breast | 2023-06-16 | 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 843207). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 446 of the CHEK2 protein (p.Asn446Ser). |
| Ambry Genetics | RCV002379525 | SCV002694508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-01 | criteria provided, single submitter | clinical testing | The p.N446S variant (also known as c.1337A>G), located in coding exon 11 of the CHEK2 gene, results from an A to G substitution at nucleotide position 1337. The asparagine at codon 446 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |