Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700322 | SCV000829072 | uncertain significance | Familial cancer of breast | 2019-12-04 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. ClinVar contains an entry for this variant (Variation ID: 577537). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 370 of the CHEK2 protein (p.Gly370Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Ambry Genetics | RCV002458281 | SCV002739838 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-17 | criteria provided, single submitter | clinical testing | The p.G370R variant (also known as c.1108G>A), located in coding exon 10 of the CHEK2 gene, results from a G to A substitution at nucleotide position 1108. The glycine at codon 370 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well 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 this alteration remains unclear. |