Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001027013 | SCV001189500 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-02 | criteria provided, single submitter | clinical testing | The p.P266T variant (also known as c.796C>A), located in coding exon 6 of the CHEK2 gene, results from a C to A substitution at nucleotide position 796. The proline at codon 266 is replaced by threonine, an amino acid with highly 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 | RCV001349684 | SCV001544039 | uncertain significance | Familial cancer of breast | 2020-04-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 827367). This sequence change replaces proline with threonine at codon 266 of the CHEK2 protein (p.Pro266Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. |
Fulgent Genetics, |
RCV002481838 | SCV002788604 | uncertain significance | Familial cancer of breast; Li-Fraumeni syndrome 2; Bone osteosarcoma; Malignant tumor of prostate; Colorectal cancer | 2021-10-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003411955 | SCV004113043 | uncertain significance | CHEK2-related condition | 2022-12-08 | criteria provided, single submitter | clinical testing | The CHEK2 c.796C>A variant is predicted to result in the amino acid substitution p.Pro266Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/827367). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |