Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000527786 | SCV000635113 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-02-14 | criteria provided, single submitter | clinical testing | This variant is a gross duplication of the genomic region encompassing exon 19 of the BRCA1 gene. While the exact position of the duplicated exon cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. Duplications of exon 19 have been reported in individuals and families with breast and/or ovarian cancer (PMID: 16715518, 16793929). Duplication of exon 19 is also known as duplication of exon 20 by legacy exon numbering in the literature. ClinVar contains an entry for duplications of exon 19 (Variation ID: 267581). The C-terminal region of the BRCA1 protein contains two BRCT repeats (BRCT-N and BRCT-C), which are essential for BRCA1 protein function (PMID: 10811118, 8751436). Structural and functional analyses have shown that the tandem BRCT domains form a well-organized structure crucial for BRCA1 transcriptional activity (PMID: 20516115, 11573086, 15172985). This variant is expected to disrupt the BRCT repeats, which would likely destabilize the structure of the C-terminal region of the BRCA1 protein and disrupt BRCA1 transcriptional activity. 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. |