ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5030_5033del (p.Thr1677fs) (rs80357580)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162882 SCV000213369 pathogenic Hereditary cancer-predisposing syndrome 2017-12-08 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) RCV000031204 SCV000145266 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162882 SCV000683243 pathogenic Hereditary cancer-predisposing syndrome 2015-06-09 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031204 SCV000326110 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031204 SCV000785273 pathogenic Breast-ovarian cancer, familial 1 2017-06-27 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031204 SCV000744603 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031204 SCV000564386 pathogenic Breast-ovarian cancer, familial 1 2016-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048741 SCV000591562 pathogenic Hereditary breast and ovarian cancer syndrome 2013-08-06 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031204 SCV000300187 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735512 SCV000863650 pathogenic Breast and/or ovarian cancer 2013-11-04 no assertion criteria provided clinical testing
GeneDx RCV000236835 SCV000292525 pathogenic not provided 2017-03-14 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.5030_5033delCTAA at the cDNA level and p.Thr1677IlefsX2 (T1677IfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TTAA[delCTAA]TCTA. The deletion causes a frameshift, which changes a Threonine to an Isoleucine at codon 1677, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.5030_5033delCTAA, also known as 5149del4 by alternate nomenclature, has been identified in several hereditary breast cancer families (Stoppa-Lyonnet 1997, Schneegans 2012, de Juan Jimenez 2013, Kang 2015, Solano 2015). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048741 SCV000916746 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-07 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5030_5033delCTAA (p.Thr1677IlefsX2) 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 246178 control chromosomes. The c.5030_5033delCTAA variant has been reported in the literature in numerous individuals affected with Hereditary Breast and Ovarian Cancer. 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. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, all of whom classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000048741 SCV000076754 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1677Ilefs*2) 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 observed in several individuals affected with breast and/or ovarian cancer, and pancreatic cancer (PMID: 9150149, 21989927, 22144684, 22160602). This variant is also known as 5149del4, ter1678 and c.5149delCTAA in the literature. ClinVar contains an entry for this variant (Variation ID: 37623). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Molecular Diagnosis of Cancer,West China Hospital, Sichuan University RCV000240792 SCV000265866 pathogenic Neoplasm of the breast 2015-11-01 criteria provided, single submitter research
Mendelics RCV000048741 SCV000839222 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031204 SCV000195936 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236835 SCV000296478 pathogenic not provided 2016-05-25 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048741 SCV000587444 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031204 SCV000053804 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing

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