ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.70_80delTGTCCCATCTG (p.Cys24Serfs) (rs80357696)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111682 SCV000282349 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000049106 SCV000077119 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change deletes 11 nucleotides from exon 2 of the BRCA1 mRNA (c.70_80delTGTCCCATCTG), causing a frameshift at codon 24. This creates a premature translational stop signal (p.Cys24Serfs*13) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This particular truncation has been reported in the literature in individuals affected with breast cancer and ovarian cancer (PMID: 7837387, 10498392, 25682074, 22711857, 2246425, 26543556). This variant is also known as 188del11 and 189del11 in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131391 SCV000186367 pathogenic Hereditary cancer-predisposing syndrome 2017-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000111682 SCV000296416 pathogenic Breast-ovarian cancer, familial 1 2015-12-18 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111682 SCV000326397 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000486060 SCV000568440 pathogenic not provided 2018-11-12 criteria provided, single submitter clinical testing This deletion of 11 nucleotides in BRCA1 is denoted c.70_80del11 at the cDNA level and p.Cys24SerfsX13(C24SfsX13) at the protein level. The surrounding sequence, with the bases that are deleted in brackets, is AGAG[del11]GTAA. The deletion causes a frameshift, which changes a Cysteine to a Serine at codon 24, and creates a premature stop codon at position 13 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.70_80del11, also defined BRCA1 189_199del11 and 188del11 using alternate nomenclature, has been observed in multiple individuals with a personal and/or family history of breast, ovarian, and/or pancreatic cancer (Friedman 1995, Shattuck-Eidens 1995, Berman 1996, Hopper 1999, Dean 2015, Shindo 2017). We consider this variant to be pathogenic.
Counsyl RCV000111682 SCV000677630 pathogenic Breast-ovarian cancer, familial 1 2017-03-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486060 SCV000887731 pathogenic not provided 2015-12-18 criteria provided, single submitter clinical testing
Color RCV000131391 SCV000909426 pathogenic Hereditary cancer-predisposing syndrome 2018-02-15 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111682 SCV000144182 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000049106 SCV000587007 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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