Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048236 | SCV001212228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-01 | criteria provided, single submitter | clinical testing | 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"). 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. This variant has not been reported in the literature in individuals with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with isoleucine at codon 1024 of the RAD50 protein (p.Leu1024Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. |
| Ambry Genetics | RCV001048236 | SCV003855369 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-10 | criteria provided, single submitter | clinical testing | The p.L1024I variant (also known as c.3070T>A), located in coding exon 20 of the RAD50 gene, results from a T to A substitution at nucleotide position 3070. The leucine at codon 1024 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |