Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001237269 | SCV001410023 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2021-03-01 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 11 (c.4097-20_4134del) of the BRCA1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has not been reported in the literature in individuals with BRCA1-related conditions. 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. |
| Ambry Genetics | RCV002322134 | SCV002628350 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The c.4097-20_4134del58 variant results from a deletion of 58 nucleotides between positions c.4097-20 and c.4134 and involves the canonical splice acceptor site before coding exon 10 of the BRCA1 gene. The canonical splice acceptor site is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478745 | SCV004219388 | likely pathogenic | not provided | 2023-05-09 | criteria provided, single submitter | clinical testing | This variant disrupts a canonical splice-acceptor site and is predicted to interfere with normal BRCA1 mRNA splicing. The variant has not been reported in individuals with BRCA1-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic. |