Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222072 | SCV000275266 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-05-01 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence |
| Invitae | RCV000222072 | SCV000547975 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-09 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with serine at codon 569 of the RAD50 protein (p.Tyr569Ser). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 231421). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |