Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000638038 | SCV000759518 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-01-24 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exons 4-12 of the BRCA1 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. Similar duplications encompassed by this larger event have been reported in individuals affected with breast and/or ovarian cancer (PMID: 26271414, 24825132, 10827109, 22544547). Specifically, duplications of exon 12, also known as exon 13 in the literature, have been identified in several families, and are considered a common BRCA1 founder mutation in diverse populations (PMID: 9915971, 10827109, 20232141, 15951973). Sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). 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. |