Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000549208 | SCV000628156 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAD50-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 457378). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 46 of the RAD50 protein (p.Ile46Thr). |
Ambry Genetics | RCV000549208 | SCV002696452 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-13 | criteria provided, single submitter | clinical testing | The p.I46T variant (also known as c.137T>C), located in coding exon 2 of the RAD50 gene, results from a T to C substitution at nucleotide position 137. The isoleucine at codon 46 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |