Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204642 | SCV000259940 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-11 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs763571038, gnomAD 0.01%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 219842). This missense change has been observed in individual(s) with breast cancer (PMID: 25503501). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 560 of the RAD50 protein (p.Ser560Ile). |
| Ambry Genetics | RCV000204642 | SCV000671845 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-06-22 | criteria provided, single submitter | clinical testing | The p.S560I variant (also known as c.1679G>T), located in coding exon 11 of the RAD50 gene, results from a G to T substitution at nucleotide position 1679. The serine at codon 560 is replaced by isoleucine, an amino acid with dissimilar properties. This alteration was previously reported in at least one individual from a cohort of 278 BRCA1/2-negative individuals with early-onset breast cancer via multiplex panel testing of 22 cancer susceptibility genes. (Maxwell KN et al. Genet. Med., 2015 Aug;17:630-8). This amino acid position is not 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. |