Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000144594 | SCV001569144 | uncertain significance | Familial cancer of breast | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 306 of the CHEK2 protein (p.Gly306Arg). 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: 156500). 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. |
| Gene |
RCV002277285 | SCV002567705 | uncertain significance | not provided | 2022-02-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 22419737, 19782031) |
| Ambry Genetics | RCV002371982 | SCV002688661 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-14 | criteria provided, single submitter | clinical testing | The p.G306R variant (also known as c.916G>A), located in coding exon 8 of the CHEK2 gene, results from a G to A substitution at nucleotide position 916. The glycine at codon 306 is replaced by arginine, an amino acid with dissimilar 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. |
| Pathway Genomics | RCV000144594 | SCV000189920 | uncertain significance | Familial cancer of breast | 2014-07-24 | no assertion criteria provided | clinical testing |