ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.303T>G (p.Tyr101Ter) (rs80356936)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162861 SCV000213348 pathogenic Hereditary cancer-predisposing syndrome 2017-09-26 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) RCV000112260 SCV000144982 pathogenic Breast-ovarian cancer, familial 1 2007-01-18 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112260 SCV000325542 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) RCV000112260 SCV000299438 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 RCV000074578 SCV000108663 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.303T>G at the cDNA level and p.Tyr101Ter (Y101X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAT>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with hereditary breast and/or ovarian cancer, and has been found to be a recurrent variant in individuals of African ancestry (Russo 2007, Veschi 2007, Zhang 2009, Zhang 2012). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048054 SCV000698998 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.303T>G (p.Tyr101X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 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 (e.g. p.Glu143X, p.Tyr261X). Mutation taster predicts a damaging outcome for this variant. This variant is absent in 120796 control chromosomes while it was reported in several breast cancer patients indicating causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000048054 SCV000076067 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr101*) 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 ovarian cancer (PMID: 17221156, 18679828, 26681312). ClinVar contains an entry for this variant (Variation ID: 54758). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048054 SCV000587045 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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