Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001182382 | SCV001347817 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-21 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with isoleucine at codon 291 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. |
Ambry Genetics | RCV001182382 | SCV002685272 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-27 | criteria provided, single submitter | clinical testing | The p.F291I variant (also known as c.871T>A), located in coding exon 7 of the CHEK2 gene, results from a T to A substitution at nucleotide position 871. The phenylalanine at codon 291 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is 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. |
Invitae | RCV002559024 | SCV003242726 | uncertain significance | Familial cancer of breast | 2022-10-25 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 922350). 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 phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 291 of the CHEK2 protein (p.Phe291Ile). |
Prevention |
RCV003983844 | SCV004797602 | uncertain significance | CHEK2-related condition | 2023-12-21 | criteria provided, single submitter | clinical testing | The CHEK2 c.871T>A variant is predicted to result in the amino acid substitution p.Phe291Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. It is interpreted as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/922350/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |