Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001325261 | SCV001516246 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-04 | 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 (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. 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 isoleucine with valine at codon 761 of the RAD50 protein (p.Ile761Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |
Ambry Genetics | RCV001325261 | SCV002732260 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-04 | criteria provided, single submitter | clinical testing | The p.I761V variant (also known as c.2281A>G), located in coding exon 14 of the RAD50 gene, results from an A to G substitution at nucleotide position 2281. The isoleucine at codon 761 is replaced by valine, 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. |
Baylor Genetics | RCV003462898 | SCV004207322 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-10-11 | criteria provided, single submitter | clinical testing |