Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032316 | SCV001195623 | pathogenic | Hereditary breast ovarian cancer syndrome | 2021-08-02 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 4-23 of the BRCA1 gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant eliminates approximately 97% of the BRCA1 protein including critical domains for nuclear localization and the C-terminal BRCT domains (PMID: 20104584). 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. For these reasons, this variant has been classified as Pathogenic. |