ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3178G>T (p.Glu1060Ter) (rs80357424)

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Total submissions: 13
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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) RCV000077540 SCV000299891 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048092 SCV000076105 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1060*) 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: 9333265, 24010542, 26681312). This variant is also known as 3297G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 54789). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000077540 SCV000195916 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000212171 SCV000210143 pathogenic not provided 2014-01-20 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3178G>T at the cDNA level and p.Glu1060Stop (E1060X) at the protein level. The substitution creates a nonsense variant, changing a Glutamic Acid to a premature stop codon (GAA>TAA). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also denoted BRCA1 3297G>T using alternative nomenclature, has been reported in assocation with breast cancer (Shattuck-Eidens 1997, Fostira 2005). BRCA1 E1060X has also been listed >10 times in the Breast Cancer Information Core (BIC) database as clinically important.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077540 SCV000325570 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000448786 SCV000537659 pathogenic Hereditary cancer-predisposing syndrome 2015-09-16 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077540 SCV000564339 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212171 SCV000600319 pathogenic not provided 2017-06-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000448786 SCV000660945 pathogenic Hereditary cancer-predisposing syndrome 2017-07-14 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),Rarity in general population databases (dbsnp, esp, 1000 genomes)
Integrated Genetics/Laboratory Corporation of America RCV000048092 SCV000918719 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3178G>T (p.Glu1060X) 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 245534 control chromosomes (gnomAD). The variant, c.3178G>T, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (e.g. Shattuck-Eidens_1997, Loman_2001, Moller_2001, Fostira_2014). 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. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077540 SCV000109341 pathogenic Breast-ovarian cancer, familial 1 2007-02-02 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077540 SCV000144653 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048092 SCV000587283 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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