Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799895 | SCV000939579 | uncertain significance | Familial cancer of breast | 2023-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 321 of the CHEK2 protein (p.Glu321Lys). 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: 645746). 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: 16835864). 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. |
| Ambry Genetics | RCV002370111 | SCV002689011 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-16 | criteria provided, single submitter | clinical testing | The p.E321K variant (also known as c.961G>A), located in coding exon 8 of the CHEK2 gene, results from a G to A substitution at nucleotide position 961. The glutamic acid at codon 321 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual diagnosed with prostate cancer (Wu X et al. Hum Mutat, 2006 Aug;27:742-7). 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. |