Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000532614 | SCV000628315 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln226*) in the RAD50 gene. RNA analysis indicates that this premature translational stop signal induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs377429225, gnomAD 0.002%). 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: 457485). Studies have shown that this premature translational stop signal results in skipping of exon 5 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000532614 | SCV001187855 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-06 | criteria provided, single submitter | clinical testing | The p.Q226* pathogenic mutation (also known as c.676C>T), located in coding exon 5 of the RAD50 gene, results from a C to T substitution at nucleotide position 676. This changes the amino acid from a glutamine to a stop codon within coding exon 5. 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 | RCV003470724 | SCV004207440 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2022-05-28 | criteria provided, single submitter | clinical testing |