ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3904G>T (p.Glu1302Ter) (rs80357461)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569716 SCV000665797 pathogenic Hereditary cancer-predisposing syndrome 2018-02-21 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) RCV000083199 SCV000144914 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000569716 SCV000909286 pathogenic Hereditary cancer-predisposing syndrome 2018-10-16 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083199 SCV000325782 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) RCV000083199 SCV000300040 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 RCV000484534 SCV000567704 pathogenic not provided 2016-07-08 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.3904G>T at the cDNA level and p.Glu1302Ter (E1302X) 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 mutation, previously published as BRCA1 4023G>T, has been reported in individuals with personal and/or family history of breast and/or ovarian cancer and is considered pathogenic (Casadei 2001, Judkins 2005, Ramus 2007, Nielsen 2016).
Integrated Genetics/Laboratory Corporation of America RCV000496224 SCV000918798 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-06 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3904G>T (p.Glu1302X) 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.3937C>T (p.Gln1313X), c.4015G>T (p.Glu1339X), c.4035delA (p.Glu1346fsX20)). The variant was absent in 245896 control chromosomes (gnomAD). c.3904G>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Rebbeck_2018, Lecarpentier_2012, Ramus_2007, Judkins_2005, Sirchia_2005). These data indicate that the variant is very likely to be associated with disease. Four ClinVar submissions from clinical diagnostic laboratories and reputable databases (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496224 SCV000587357 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000083199 SCV000115273 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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