Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166807 | SCV000217621 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-24 | criteria provided, single submitter | clinical testing | The p.R138* pathogenic mutation (also known as c.412C>T), located in coding exon 4 of the RAD50 gene, results from a C to T substitution at nucleotide position 412. This changes the amino acid from an arginine to a stop codon within coding exon 4. This mutation has been identified in a patient with breast cancer, and was called a novel pathogenic mutation by the study authors (Guan Y et al. Fam. Cancer, 2015 Mar;14:9-18). 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. |
Invitae | RCV000166807 | SCV000547971 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg138*) 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 (rs786203485, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 24894818, 25151137). ClinVar contains an entry for this variant (Variation ID: 187117). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003462225 | SCV004207340 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2023-09-12 | criteria provided, single submitter | clinical testing |