Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014410 | SCV001175110 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-07 | criteria provided, single submitter | clinical testing | The p.I698M variant (also known as c.2094C>G), located in coding exon 13 of the RAD50 gene, results from a C to G substitution at nucleotide position 2094. The isoleucine at codon 698 is replaced by methionine, an amino acid with highly similar 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. |
| Invitae | RCV001014410 | SCV001562130 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 820702). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 698 of the RAD50 protein (p.Ile698Met). |