Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822634 | SCV000963444 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD50-related disease. This sequence change replaces proline with serine at codon 734 of the RAD50 protein (p.Pro734Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV000822634 | SCV001175503 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-04-02 | criteria provided, single submitter | clinical testing | The p.P734S variant (also known as c.2200C>T), located in coding exon 13 of the RAD50 gene, results from a C to T substitution at nucleotide position 2200. The proline at codon 734 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |