Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000205611 | SCV000259631 | uncertain significance | Familial cancer of breast | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 49 of the CHEK2 protein (p.Ser49Phe). 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: 219642). 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. |
| Ambry Genetics | RCV000561755 | SCV000676010 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-16 | criteria provided, single submitter | clinical testing | The p.S49F variant (also known as c.146C>T), located in coding exon 1 of the CHEK2 gene, results from a C to T substitution at nucleotide position 146. The serine at codon 49 is replaced by phenylalanine, an amino acid with highly dissimilar 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. |
| Color Diagnostics, |
RCV000561755 | SCV000684599 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-06 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 49 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. |
| Prevention |
RCV000679675 | SCV000806871 | uncertain significance | not provided | 2017-11-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000679675 | SCV002499831 | uncertain significance | not provided | 2023-07-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22114986, 11733767, 29641532, 34480478) |
| Baylor Genetics | RCV000205611 | SCV004217526 | uncertain significance | Familial cancer of breast | 2023-10-01 | criteria provided, single submitter | clinical testing |