BRCA1 NM_007294.3:c.68_69del, Glu23ValfsTer17

""

Error in OpenAI Consolidation. OncoKB: BRCA1E23Vfs*17BRCA1E23Vfs*17SomaticNCBI Gene:672|Show additional gene information Variant OverviewBRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.The BRCA1 E23Vfs*17 mutation is known to be oncogenic.Hide mutation effect description The mutation effect description for E23fs in BRCA1 is: The BRCA1 E23fs mutation is located in the RING domain of the protein. It is a known deleterious mutation in BRCA1 that abolishes the RING-domain of the protein (PMID: 23867111, 15569676, 14729053). BRCA1 E23fs carries an associated risk of 56% for breast cancer, 16% for ovarian cancer and 16% for prostate cancer by age 70 (PMID: 9145676) and is one of the most common Ashkenazi Jewish BRCA1 founder mutations (PMID: 14576434). Modeling of this variant in mice via a BRCA1 185stop mutation demonstrated that this variant not only predisposed animals to mammary tumors but also compromised response to treatment with platinum drugs and PARP inhibitors (PMID: 27454287). In vitro studies with MCF-10A cells expressing this mutation have demonstrated that it is inactivating as measured by increased radiosensitivity, chromosomal instability, polyploid fractions and centrosome number compared to wildtype (PMID: 26246475). In vitro studies in cancer cells harboring RING-less BRCA1 also demonstrated that loss of the RING domain can confer resistance to PARP inhibitors and platinum agents (PMID: 27454289). JAX-CKB: No results found