Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013365 | SCV001173944 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-14 | criteria provided, single submitter | clinical testing | The p.E614Q variant (also known as c.1840G>C), located in coding exon 12 of the RAD50 gene, results from a G to C substitution at nucleotide position 1840. The glutamic acid at codon 614 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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 | RCV001013365 | SCV002212366 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 614 of the RAD50 protein (p.Glu614Gln). ClinVar contains an entry for this variant (Variation ID: 820170). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. |