ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.412C>T (p.Arg138Ter)

gnomAD frequency: 0.00003  dbSNP: rs786203485
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Total submissions: 3
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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

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