Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164290 | SCV000214917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | The p.R1279C variant (also known as c.3835C>T), located in coding exon 25 of the RAD50 gene, results from a C to T substitution at nucleotide position 3835. The arginine at codon 1279 is replaced by cysteine, an amino acid with highly dissimilar properties. Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000164290 | SCV000628292 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1279 of the RAD50 protein (p.Arg1279Cys). This variant is present in population databases (rs786201810, gnomAD 0.006%). 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: 184946). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Baylor Genetics | RCV003467288 | SCV004207344 | uncertain significance | Nijmegen breakage syndrome-like disorder | 2023-09-07 | criteria provided, single submitter | clinical testing |