Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001057805 | SCV001222320 | uncertain significance | Familial cancer of breast | 2023-04-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CHEK2-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 853065). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 57 of the CHEK2 protein (p.Ser57Cys). |
| Ambry Genetics | RCV002400330 | SCV002714563 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-05 | criteria provided, single submitter | clinical testing | The p.S57C variant (also known as c.170C>G), located in coding exon 1 of the CHEK2 gene, results from a C to G substitution at nucleotide position 170. The serine at codon 57 is replaced by cysteine, 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. |
| Baylor Genetics | RCV001057805 | SCV004217632 | uncertain significance | Familial cancer of breast | 2023-07-14 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV002400330 | SCV004361412 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-09 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with cysteine at codon 57 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 CHEK2-related disorders 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. |