Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018415 | SCV001179651 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-27 | criteria provided, single submitter | clinical testing | The p.E295D variant (also known as c.885A>T), located in coding exon 7 of the CHEK2 gene, results from an A to T substitution at nucleotide position 885. The glutamic acid at codon 295 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001059186 | SCV001223800 | uncertain significance | Familial cancer of breast | 2023-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 295 of the CHEK2 protein (p.Glu295Asp). This variant is not present in population databases (gnomAD no frequency). 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: 822778). 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. 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. |
| Baylor Genetics | RCV001059186 | SCV004217572 | uncertain significance | Familial cancer of breast | 2023-09-05 | criteria provided, single submitter | clinical testing |