Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549392 | SCV000635112 | pathogenic | Hereditary breast ovarian cancer syndrome | 2017-03-03 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing most of exon 19 of the BRCA1 gene, including the exon 19-intron 19 boundary, and ~3,200 nucleotides of intron 19 (c.5213_5278-2753del). This may create a premature translational stop signal that would be expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). Similar partial deletions of exon 19, also known as exon 20 in the literature, have been reported in families affected with breast and ovarian cancer (PMID: 20840220, 15353005). In one family, the variant segregated with breast cancer in 5 affected individuals. Experimental RT-PCR analysis showed the absence of this entire exon in the mRNA of an affected carrier (PMID: 15353005). The complete in-frame loss of exon 19 (His1732-Lys1759) is expected to remove the linker region between the two BRCT domains, which are known to be important for BRCA1 protein structure and function (PMID: 20516115). For these reasons, this variant has been classified as Pathogenic. |