Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574623 | SCV000666388 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-19 | criteria provided, single submitter | clinical testing | The p.L191V variant (also known as c.571C>G), located in coding exon 3 of the CHEK2 gene, results from a C to G substitution at nucleotide position 571. The leucine at codon 191 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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 | RCV001064430 | SCV001229333 | uncertain significance | Familial cancer of breast | 2023-07-15 | criteria provided, single submitter | clinical testing | 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: 481732). 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. This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 191 of the CHEK2 protein (p.Leu191Val). |