ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3331_3334del (p.Gln1111fs) (rs80357701)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000413338 SCV000492471 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000131812 SCV000186867 pathogenic Hereditary cancer-predisposing syndrome 2017-08-01 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) RCV000031104 SCV000144725 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770743 SCV000902226 pathogenic Breast and/or ovarian cancer 2016-01-21 criteria provided, single submitter clinical testing
Color RCV000131812 SCV000683099 pathogenic Hereditary cancer-predisposing syndrome 2016-09-23 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031104 SCV000325616 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031104 SCV000220251 pathogenic Breast-ovarian cancer, familial 1 2014-04-18 criteria provided, single submitter literature only
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031104 SCV000744636 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031104 SCV000564303 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000195363 SCV000591438 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031104 SCV000733628 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000031104 SCV000700165 pathogenic Breast-ovarian cancer, familial 1 2016-10-04 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031104 SCV000282303 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000048151 SCV000210038 pathogenic not provided 2018-08-13 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA1 is denoted c.3331_3334delCAAG at the cDNA level and p.Gln1111AsnfsX5 (Q1111NfsX5) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAAG[delCAAG]AATA. The deletion causes a frameshift, which changes a Glutamine to an Asparagine at codon 1111, and creates a premature stop codon at position 5 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.3331_3334delCAAG, previously reported as 3450del4 or 3450delCAAG using alternate nomenclature, has been reported in patients with personal and/or family histories of breast and/or ovarian cancer, segregating with cancer in at least one family, and likely represents a Spanish founder variant (Durocher 1996, Panguluri 1999, Torres 2007, Zhang 2011, Rodriguez 2012, Blay 2013, Laraqui 2013, Felix 2014, Peixoto 2014, Fernandes 2016, Maistro 2016). An in vitro functional assay demonstrated that this variant affects cell cycle progression, cell motility, and invasion in breast epithelial cells, thus supporting a role in breast cancer progression (Yasmeen 2008). We consider this variant to be pathogenic.
GeneKor MSA RCV000048151 SCV000693526 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000195363 SCV000699020 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-22 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3331_3334delCAAG (p.Gln1111Aspfs) 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.3342_3345delAGAA [p.Glu1115X], c.3351dupT [p.Gln1118fs). One in silico tool, Mutation Taster, predicts a damaging outcome for this variant. This variant is absent in the large control population database ExAC (0/121128 control chromosomes). Multiple clinical diagnostic laboratories/reputable databases (13 in total) classified this variant as pathogenic. Additionally, several publications have identified the variant in affected individuals and co-segregation of the variant with disease has been established through family studies. Taken together, this variant is classified as pathogenic.
Invitae RCV000195363 SCV000076164 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1111Asnfs*5) 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 as a common cause of hereditary breast and ovarian cancer in Colombian and Portuguese populations (PMID: 22044689, 24742220, 24916970). This variant is also known as 3450del4 and 3450delCAAG in the literature. ClinVar contains an entry for this variant (Variation ID: 37523). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000195363 SCV000839256 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031104 SCV000195918 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048151 SCV000296361 pathogenic not provided 2015-07-08 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000195363 SCV000587299 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031104 SCV000053700 pathogenic Breast-ovarian cancer, familial 1 2012-02-28 no assertion criteria provided clinical testing

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