Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001188620 | SCV001355704 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-04 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with threonine at codon 240 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV002560027 | SCV003312424 | uncertain significance | Familial cancer of breast | 2023-05-15 | criteria provided, single submitter | clinical testing | 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 arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 240 of the CHEK2 protein (p.Arg240Thr). ClinVar contains an entry for this variant (Variation ID: 926206). 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. 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. |
Ambry Genetics | RCV001188620 | SCV004006472 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-21 | criteria provided, single submitter | clinical testing | The p.R240T variant (also known as c.719G>C), located in coding exon 5 of the CHEK2 gene, results from a G to C substitution at nucleotide position 719. The arginine at codon 240 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |