ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3257T>G (p.Leu1086Ter) (rs80357006)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000414138 SCV000492452 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000131910 SCV000186965 pathogenic Hereditary cancer-predisposing syndrome 2018-01-31 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) RCV000083194 SCV000144691 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131910 SCV000909312 pathogenic Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083194 SCV000325589 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000083194 SCV000299903 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657619 SCV000779362 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3257T>G at the cDNA level and p.Leu1086Ter (L1086X) at the protein level. The substitution creates a nonsense variant, which changes a Leucine to a premature stop codon (TTA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3257T>G, previously reported as BRCA1 3376T>G using alternate nomenclature, has been reported in multiple families with breast and/or ovarian cancer (Wagner 1998, Llort 2002, Beristain 2010, de Juan Jim?nez 2013, Silva 2014, Minucci 2015) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048114 SCV000916708 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-19 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3257T>G (p.Leu1086X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.3288_3289delAA/p.Leu1098fsX4, c.3340G>T/p.Glu1114X, etc). The variant was absent in 245296 control chromosomes. c.3257T>G has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. 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. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000048114 SCV000076127 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1086*) 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/or ovarian cancer (PMID: 9663595, 11857748, 23479189, 24884479, 24916970). This variant is also known as 3376T>G in the literature. ClinVar contains an entry for this variant (Variation ID: 54810). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000048114 SCV000839257 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048114 SCV000587293 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000083194 SCV000115268 pathogenic Breast-ovarian cancer, familial 1 2010-12-06 no assertion criteria provided clinical testing

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