Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000474200 | SCV000550546 | uncertain significance | Familial cancer of breast | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 250 of the CHEK2 protein (p.Ile250Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 410060). 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. 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 | RCV000563163 | SCV000673250 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-09 | criteria provided, single submitter | clinical testing | The p.I250T variant (also known as c.749T>C), located in coding exon 5 of the CHEK2 gene, results from a T to C substitution at nucleotide position 749. The isoleucine at codon 250 is replaced by threonine, 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 tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282155 | SCV002570838 | uncertain significance | not specified | 2022-07-17 | criteria provided, single submitter | clinical testing |