Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164160 | SCV000214776 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-11-23 | criteria provided, single submitter | clinical testing | The p.E247G variant (also known as c.740A>G), located in coding exon 5 of the RAD50 gene, results from an A to G substitution at nucleotide position 740. The glutamic acid at codon 247 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000164160 | SCV000628319 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-10 | 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: "Benign"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 184834). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 247 of the RAD50 protein (p.Glu247Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. |