Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000706585 | SCV000835644 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1104 of the RAD50 protein (p.Tyr1104Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 582497). 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 expected to disrupt RAD50 protein function. 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. |
| Ambry Genetics | RCV000706585 | SCV001181316 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-03 | criteria provided, single submitter | clinical testing | The p.Y1104C variant (also known as c.3311A>G), located in coding exon 21 of the RAD50 gene, results from an A to G substitution at nucleotide position 3311. The tyrosine at codon 1104 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was reported in a study of 1297 cases of early-onset breast cancer and 1121 controls (Young EL et al. J Med Genet, 2016 Jun;53:366-76). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003460985 | SCV004207387 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-06-22 | criteria provided, single submitter | clinical testing |