ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4117G>T (p.Glu1373Ter) (rs80357259)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162872 SCV000213359 pathogenic Hereditary cancer-predisposing syndrome 2017-12-24 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) RCV000031150 SCV000144987 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162872 SCV000537657 pathogenic Hereditary cancer-predisposing syndrome 2016-03-28 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031150 SCV000325854 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031150 SCV000677652 pathogenic Breast-ovarian cancer, familial 1 2015-09-11 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048449 SCV000591492 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-05 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031150 SCV000300075 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735478 SCV000863615 pathogenic Breast and/or ovarian cancer 2002-03-21 no assertion criteria provided clinical testing
GeneDx RCV000074589 SCV000108674 pathogenic not provided 2019-01-04 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.4117G>T at the cDNA level and p.Glu1373Ter (E1373X) at the protein level. Using alternate nomenclature this variant would be defined as BRCA1 4236G>T. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple families with clinical histories consistent with hereditary breast and ovarian cancer syndrome (Nedelcu 2002, Kadouri 2007, Veschi 2007, Grant 2015, Lolas Hamameh 2017). We consider this variant to be pathogenic.
Invitae RCV000048449 SCV000076462 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1373*) 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 affected with breast and ovarian cancer (PMID: 17591842, 11179017, 26219728). This variant is also known as 4236G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37569). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048449 SCV000587375 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031150 SCV000053750 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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