Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213517 | SCV000275467 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-15 | criteria provided, single submitter | clinical testing | The p.F169L variant (also known as c.507T>G), located in coding exon 3 of the CHEK2 gene, results from a T to G substitution at nucleotide position 507. The phenylalanine at codon 169 is replaced by leucine, an amino acid with highly similar 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. |
Color Diagnostics, |
RCV000213517 | SCV000913988 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-17 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with leucine at codon 169 of the CHEK2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 been identified in 2/251418 chromosomes 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 | RCV001036467 | SCV001199833 | uncertain significance | Familial cancer of breast | 2023-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 169 of the CHEK2 protein (p.Phe169Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 231571). 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. Experimental studies have shown that this missense change affects CHEK2 function (PMID: 34903604). 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. |
Institute for Clinical Genetics, |
RCV001729467 | SCV002009492 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Clinical Genetics Laboratory, |
RCV001729467 | SCV001977639 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Diagnostic Laboratory, |
RCV001729467 | SCV001978543 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001729467 | SCV001979357 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001729467 | SCV001980135 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001729467 | SCV002035212 | uncertain significance | not provided | no assertion criteria provided | clinical testing |