ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3759dupT (p.Lys1254Terfs) (rs80357687)

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Total submissions: 11
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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) RCV000077130 SCV000300006 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 RCV000048318 SCV000076331 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1254*) 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: 9523200, 10528853, 23479189). This variant is also known as 3879insT or c.3759_3760insT in the literature. ClinVar contains an entry for this variant (Variation ID: 54992). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000164495 SCV000215144 pathogenic Hereditary cancer-predisposing syndrome 2017-10-05 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077130 SCV000296359 pathogenic Breast-ovarian cancer, familial 1 2015-07-08 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077130 SCV000325745 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000048318 SCV000588049 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048318 SCV000699071 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3759dupT (p.Lys1254X) 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.c.4222C>T/p.Gln1408X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121388 control chromosomes. This variant has been reported in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Color RCV000164495 SCV000905050 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077130 SCV000108927 pathogenic Breast-ovarian cancer, familial 1 2008-03-26 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077130 SCV000144864 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 RCV000048318 SCV000587343 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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