Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571472 | SCV000666390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-23 | criteria provided, single submitter | clinical testing | The p.D311H variant (also known as c.931G>C), located in coding exon 8 of the CHEK2 gene, results from a G to C substitution at nucleotide position 931. The aspartic acid at codon 311 is replaced by histidine, 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002476225 | SCV002774544 | uncertain significance | not provided | 2021-08-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002526829 | SCV003297052 | uncertain significance | Familial cancer of breast | 2023-09-27 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 481734). 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 aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 311 of the CHEK2 protein (p.Asp311His). 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. |