Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556804 | SCV000633192 | uncertain significance | Familial cancer of breast | 2017-04-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with glutamine at codon 161 of the CHEK2 protein (p.Glu161Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. In summary, this variant is a novel missense change with uncertain impact on protein function. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CHEK2-related disease. |
| Ambry Genetics | RCV001023111 | SCV001184937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-20 | criteria provided, single submitter | clinical testing | The p.E161Q variant (also known as c.481G>C), located in coding exon 3 of the CHEK2 gene, results from a G to C substitution at nucleotide position 481. The glutamic acid at codon 161 is replaced by glutamine, 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. |