Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000532951 | SCV000635122 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon 3 of the BRCA1 gene. While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679). This variant would be expected to be in-frame, preserving the integrity of the reading frame. A similar duplication of exon 3 in BRCA1 (3 copies) has been observed in an individual affected with breast cancer (PMID: 20451485). ClinVar contains an entry for this variant (Variation ID: 267621). Multiple missense variants in this region have been reported to affect BRCA1 protein function (PMID: 30209399). This observation suggests that structural disruption of this region may affect BRCA1 protein function. If this copy number gain occurs in tandem, it will disrupt the integrity of the BRCA1 RING domain, which is essential for BRCA1 protein function (PMID: 11573085, 25652403, 20029420). 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. |