Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000469803 | SCV000548049 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys722Asnfs*6) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). This variant is present in population databases (rs587781454, gnomAD 0.02%). 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: 408395). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000469803 | SCV000667004 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-05 | criteria provided, single submitter | clinical testing | The c.2165_2166insT pathogenic mutation, located in coding exon 13 of the RAD50 gene, results from an insertion of one nucleotide at position 2165, causing a translational frameshift with a predicted alternate stop codon (p.K722Nfs*6). This variant has been identified in at least two patients with a personal and family history of breast and/or ovarian cancer (Maxwell KN et al. Am. J. Hum. Genet. 2016 May;98:801-817; Chan GHJ et al. Oncotarget. 2018 Jul;9:30649-30660). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV003463902 | SCV004207362 | pathogenic | Nijmegen breakage syndrome-like disorder | 2023-07-26 | criteria provided, single submitter | clinical testing |