ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.188T>A (p.Leu63Ter) (rs80357086)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 17
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077499 SCV000282266 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 RCV000047620 SCV000075633 pathogenic Hereditary breast and ovarian cancer syndrome 2018-06-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu63*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80357086, ExAC 0.002%). This variant has been reported in the literature in individuals affected with breast and/or ovarian cancer (PMID: 25802882, 15168169, 26187060, 19016756, 24249303, 26439132, 24884479, 7627958). This variant is also known as a common cause of breast and/or ovarian cancer in the Japanese populations (PMID: 24249303, 26187060). ClinVar contains an entry for this variant (Variation ID: 54381). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000162847 SCV000213334 pathogenic Hereditary cancer-predisposing syndrome 2018-02-07 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)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077499 SCV000325166 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000413802 SCV000492460 pathogenic Neoplasm of the breast criteria provided, single submitter research
Department of Medical Genetics,Oslo University Hospital RCV000077499 SCV000564384 pathogenic Breast-ovarian cancer, familial 1 2016-03-22 criteria provided, single submitter clinical testing
GeneDx RCV000478996 SCV000568435 pathogenic not provided 2017-05-11 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.188T>A at the cDNA level and p.Leu63Ter (L63X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as 307T>A using alternate nomenclature, has been reported in individuals with breast and/or ovarian cancer and is considered a Japanese pathogenic founder variant (Inoue 1995, Sekine 2001, Sugano 2008, Hirotsu 2015, Nakamura 2015). We consider BRCA1 Leu63Ter to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000478996 SCV000600271 pathogenic not provided 2017-01-21 criteria provided, single submitter clinical testing
Color RCV000162847 SCV000688351 pathogenic Hereditary cancer-predisposing syndrome 2017-08-04 criteria provided, single submitter clinical testing
Counsyl RCV000077499 SCV000786064 pathogenic Breast-ovarian cancer, familial 1 2018-02-14 criteria provided, single submitter clinical testing
Mendelics RCV000047620 SCV000839312 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047620 SCV000916711 pathogenic Hereditary breast and ovarian cancer syndrome 2017-10-26 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.188T>A (p.Leu63X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant is considered a Japanese founder variant and has been reported in several individuals with personal and family history of HBOC, and was also shown to segregate with the disease (Inoue 1995, Nakamura 2013). This variant is absent in 245910 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics RCV000077499 SCV001140643 pathogenic Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077499 SCV000109298 pathogenic Breast-ovarian cancer, familial 1 2011-09-12 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077499 SCV000144592 pathogenic Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Pathway Genomics RCV000077499 SCV000189882 pathogenic Breast-ovarian cancer, familial 1 2014-07-24 no assertion criteria provided clinical testing Japanese founder mutation.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047620 SCV000587026 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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.