Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000458096 | SCV000550458 | uncertain significance | Familial cancer of breast | 2022-02-17 | criteria provided, single submitter | clinical testing | 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 115 of the CHEK2 protein (p.Phe115Ile). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 410021). |
| Ambry Genetics | RCV001020315 | SCV001181777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-10 | criteria provided, single submitter | clinical testing | The p.F115I variant (also known as c.343T>A), located in coding exon 2 of the CHEK2 gene, results from a T to A substitution at nucleotide position 343. The phenylalanine at codon 115 is replaced by isoleucine, 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. |