Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519455 | SCV000617073 | uncertain significance | not provided | 2021-04-26 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Color Diagnostics, |
RCV000777112 | SCV000912799 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000777112 | SCV001170418 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-13 | criteria provided, single submitter | clinical testing | The p.G400W variant (also known as c.1198G>T), located in coding exon 10 of the CHEK2 gene, results from a G to T substitution at nucleotide position 1198. The glycine at codon 400 is replaced by tryptophan, an amino acid with highly dissimilar 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 | RCV001240305 | SCV001413238 | uncertain significance | Familial cancer of breast | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 400 of the CHEK2 protein (p.Gly400Trp). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 449214). 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. |