Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130723 | SCV000185610 | uncertain significance | Hereditary cancer-predisposing syndrome | 2013-11-05 | criteria provided, single submitter | clinical testing | The p.E273K variant (also known as c.817G>A) is located in coding exon 6 of the CHEK2 gene. This alteration results from a G to A substitution at nucleotide position 817. The glutamic acid at codon 273 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 8000 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.E273K remains unclear. |
| Labcorp Genetics |
RCV000791974 | SCV000931245 | uncertain significance | Familial cancer of breast | 2022-05-24 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 141973). 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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 273 of the CHEK2 protein (p.Glu273Lys). |
| Baylor Genetics | RCV000791974 | SCV005057497 | uncertain significance | Familial cancer of breast | 2024-03-29 | criteria provided, single submitter | clinical testing |