Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001020119 | SCV001181556 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-12-02 | criteria provided, single submitter | clinical testing | The p.Y1124* pathogenic mutation (also known as c.3372T>G), located in coding exon 21 of the RAD50 gene, results from a T to G substitution at nucleotide position 3372. This changes the amino acid from a tyrosine to a stop codon within coding exon 21. While this exact alteration has not been reported in the literature, a different alteration resulting in the same stop codon (c.3372T>A) has been reported in an individual diagnosed with ovarian cancer (Lilyquist J et al. Gynecol. Oncol., 2017 11;147:375-380). 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 | RCV001020119 | SCV004641524 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 823679). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26689913). This variant is present in population databases (rs775069541, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Tyr1124*) 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). |