Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167507 | SCV000218365 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-12-31 | criteria provided, single submitter | clinical testing | The p.E550Q variant (also known as c.1648G>C), located in coding exon 11 of the RAD50 gene, results from a G to C substitution at nucleotide position 1648. The glutamic acid at codon 550 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is 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 p.E550Q remains unclear. |
| Invitae | RCV000167507 | SCV001227167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-12 | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 187751). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 550 of the RAD50 protein (p.Glu550Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. |