Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694276 | SCV000822712 | uncertain significance | Familial cancer of breast | 2020-12-04 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CHEK2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 50 of the CHEK2 protein (p.Ser50Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
Ambry Genetics | RCV001011845 | SCV001172218 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-13 | criteria provided, single submitter | clinical testing | The p.S50R variant (also known as c.148A>C), located in coding exon 1 of the CHEK2 gene, results from an A to C substitution at nucleotide position 148. The serine at codon 50 is replaced by arginine, an amino acid with dissimilar 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. |
Center for Genomic Medicine, |
RCV003320478 | SCV004024670 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing |