Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000565997 | SCV000667093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-06-28 | criteria provided, single submitter | clinical testing | The p.V733A variant (also known as c.2198T>C), located in coding exon 13 of the RAD50 gene, results from a T to C substitution at nucleotide position 2198. The valine at codon 733 is replaced by alanine, 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 | RCV000565997 | SCV001395586 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-31 | criteria provided, single submitter | clinical testing | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 482154). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 733 of the RAD50 protein (p.Val733Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. |