Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573484 | SCV000667066 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-09 | criteria provided, single submitter | clinical testing | The p.R903K variant (also known as c.2708G>A), located in coding exon 16 of the RAD50 gene, results from a G to A substitution at nucleotide position 2708. The arginine at codon 903 is replaced by lysine, 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 | RCV000573484 | SCV002184125 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-23 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 482135). 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. This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 903 of the RAD50 protein (p.Arg903Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. |