Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000632220 | SCV000753359 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-27 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD50-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 57 of the RAD50 protein (p.Phe57Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. |
| Ambry Genetics | RCV000632220 | SCV002713518 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-02 | criteria provided, single submitter | clinical testing | The p.F57S variant (also known as c.170T>C), located in coding exon 2 of the RAD50 gene, results from a T to C substitution at nucleotide position 170. The phenylalanine at codon 57 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is 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. |