Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000569368 | SCV000671854 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-28 | criteria provided, single submitter | clinical testing | The p.L601I variant (also known as c.1801C>A), located in coding exon 12 of the RAD50 gene, results from a C to A substitution at nucleotide position 1801. The leucine at codon 601 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Invitae | RCV000569368 | SCV000822738 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-04-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with isoleucine at codon 601 of the RAD50 protein (p.Leu601Ile). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 484709). 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 and their clinical significance is uncertain. 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. |