Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004581235 | SCV005065329 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2024-01-18 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 19 of the BRCA1 gene. While the exact position of this variant cannot be determined from the data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant is predicted to be in-frame, and likely preserves the integrity of the reading frame. A similar copy number variant has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 16715518, 16793929). It has also been observed to segregate with disease in related individuals. This variant is also known as duplication of exon 20 by legacy exon numbering. This variant disrupts the BRCT domain, which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While functional studies have not been performed to directly test the effect of this variant on BRCA1 protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |