ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.697_698del (p.Val233fs) (rs80357747)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131861 SCV000186916 pathogenic Hereditary cancer-predisposing syndrome 2018-01-07 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031276 SCV000145667 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131861 SCV000683348 pathogenic Hereditary cancer-predisposing syndrome 2015-07-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031276 SCV000326394 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031276 SCV000564337 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031276 SCV000299475 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Integrated Genetics/Laboratory Corporation of America RCV000049102 SCV000916738 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-21 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.697_698delGT (p.Val233AsnfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 101506 control chromosomes (ExAC). The variant, c.697_698delGT, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer, predominantly in Norwegian individuals, and has been indicated to be a Norwegian founder mutation (Moller_2001). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000049102 SCV000077115 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val233Asnfs*4) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with breast, ovarian and colon cancer (PMID: 26350514, 10644434, 26822237, 22006311, 26787237) and is known to be a recurrent disease-causing variant in the Norwegian population (PMID: 14522380, 15477862, 11720839). This variant is also known as 816delGT in the literature. ClinVar contains an entry for this variant (Variation ID: 37695). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031276 SCV000296317 pathogenic Breast-ovarian cancer, familial 1 2015-03-21 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000049102 SCV000587071 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031276 SCV000053881 pathogenic Breast-ovarian cancer, familial 1 2012-08-27 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.