Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573028 | SCV000671786 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-28 | criteria provided, single submitter | clinical testing | The p.A692P variant (also known as c.2074G>C), located in coding exon 13 of the RAD50 gene, results from a G to C substitution at nucleotide position 2074. The alanine at codon 692 is replaced by proline, an amino acid with highly similar properties. Functional data using a model organism demonstrated that the p.A6992P alteration conferred sensitivity to DNA damaging agents to the same extent as the inactivation stain (Malavazi et al Mol. Microbiol. 2005 Jul;57(1):222-37). 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 | RCV000573028 | SCV002127511 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | 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. Experimental studies have shown that this variant affects RAD50 protein function (PMID: 15948962). This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 484652). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 692 of the RAD50 protein (p.Ala692Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline. |