ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1054G>T (p.Glu352Ter) (rs80357472)

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Total submissions: 8
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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) RCV000111532 SCV000299527 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000162843 SCV000213330 pathogenic Hereditary cancer-predisposing syndrome 2018-04-19 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)
GeneDx RCV000235441 SCV000292508 pathogenic not provided 2018-12-28 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.1054G>T at the cDNA level and p.Glu352Ter (E352X) 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, previously reported as BRCA1 1173G>T using alternate nomenclature, has been reported in at least four individuals with a personal and/or family history of breast and/or ovarian cancer (Sekine 2001, Simard 2007, Thirthagiri 2008, Belanger 2015) and is considered pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111532 SCV000324940 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235441 SCV000600236 pathogenic not provided 2017-03-25 criteria provided, single submitter clinical testing
Color RCV000162843 SCV000904134 pathogenic Hereditary cancer-predisposing syndrome 2017-11-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781023 SCV000918783 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-19 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1054G>T (p.Glu352X) 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 131808 control chromosomes (gnomAD). c.1054G>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Nakamura_2013, Thirthagiri_2008, Simard_2007, Sekine_2001, Lang_2017, Maxwell_2017). 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. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111532 SCV000143989 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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