ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3400G>T (p.Glu1134Ter) (rs80357018)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509963 SCV000608082 pathogenic Hereditary cancer-predisposing syndrome 2018-02-01 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) RCV000031110 SCV000144751 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000509963 SCV000688434 pathogenic Hereditary cancer-predisposing syndrome 2017-09-26 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031110 SCV000325649 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031110 SCV000564367 pathogenic Breast-ovarian cancer, familial 1 2015-07-09 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031110 SCV000282306 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000048178 SCV000209892 pathogenic not provided 2017-07-03 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3400G>T at the cDNA level and p.Glu1134Ter (E1134X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as BRCA1 3519G>T using alternate nomenclature, has been reported in individuals with early-onset and/or familial breast and ovarian cancer (Bergthorsson 2001, Nedelcu 2002, Pal 2005, Couch 2015) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000203638 SCV000699029 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-21 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a nonsense mutation involving a conserved nucleotide resulting in a predicted truncated BRCA1 protein, a known mechanism for disease. The variant of interest has not been observed in controls, but has been reported in multiple affected individuals via publications. In addition, multiple reputable databases/clinical laboratories cite the variant with a classification of "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Invitae RCV000203638 SCV000076191 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1134 (p.Glu1134*). 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 cancer and ovarian cancer (PMID: 10644434, 16284991, 25452441, 27376475, 27836010, 26833046, 11389159). This variant is also known as 3519G>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37529). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000203638 SCV000966959 pathogenic Hereditary breast and ovarian cancer syndrome 2018-01-17 criteria provided, single submitter clinical testing The p.Glu1134X variant in BRCA1 has been reported in >20 individuals with BRCA1- associated cancers (Wagner 1999, Bergthorsson 2001, Nedelcu 2002, Pal 2005, Couc h 2015, Rebbeck 2016, Breast Cancer Information Core (BIC) database: https://res earch.nhgri.nih.gov/bic/) and was absent from large population studies. This non sense variant leads to a premature termination codon at position 1134, which is predicted to lead to a truncated or absent protein. Heterozygous loss of functio n of the BRCA1 gene is an established disease mechanism in individuals with here ditary breast and ovarian cancer (HBOC). In addition, this variant was classifie d as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (C linVar SCV000282306.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon presence in m ultiple affected individuals, absence in the general population and predicted im pact to the protein. ACMG/AMP Criteria applied: PVS1; PS4; PM2 (Richards 2015).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048178 SCV000600331 pathogenic not provided 2016-11-10 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000203638 SCV000587308 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031110 SCV000053706 pathogenic Breast-ovarian cancer, familial 1 2011-12-07 no assertion criteria provided clinical testing

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