ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.1687C>T (p.Gln563Ter) (rs80356898)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 25
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031007 SCV000282262 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047559 SCV000075572 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln563*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80356898, ExAC 0.008%). This variant has been reported in many individuals with breast, ovarian, and pancreatic cancer (PMID: 23199084, 24312913, 21989927, 25330149, 25948282, 26852130). This variant is also known as 1806C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37426). Experimental studies have confirmed that this variant results in the loss of BRCA1 mRNA and protein (PMID: 12393792). 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 RCV000131897 SCV000186952 pathogenic Hereditary cancer-predisposing syndrome 2018-04-25 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)
Michigan Medical Genetics Laboratories,University of Michigan RCV000031007 SCV000195893 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000159956 SCV000210108 pathogenic not provided 2018-06-15 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1687C>T at the cDNA level and p.Gln563Ter (Q563X) at the protein level. The substitution creates a nonsense variant, changing a Glutamine to a premature stop codon (CAG>TAG). BRCA1 Gln563Ter is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also published as BRCA1 1806C>T using alternate nomenclature, has been reported in association with breast, ovarian and pancreatic cancer and is considered to be a founder pathogenic variant in Sweden and other European countries (Janavicius 2010, Ghiorzo 2012, Karami 2013, Meisel 2017). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159956 SCV000296341 pathogenic not provided 2015-05-18 criteria provided, single submitter clinical testing
GeneKor MSA RCV000238721 SCV000296792 pathogenic Ovarian cancer 2016-07-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031007 SCV000325122 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415155 SCV000492951 pathogenic Neoplasm of ovary; Breast carcinoma 2014-02-17 criteria provided, single submitter clinical testing
Color RCV000131897 SCV000537661 pathogenic Hereditary cancer-predisposing syndrome 2015-04-07 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000031007 SCV000564338 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Genologica Medica RCV000031007 SCV000577923 pathogenic Breast-ovarian cancer, familial 1 2017-01-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047559 SCV000591346 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047559 SCV000698881 pathogenic Hereditary breast and ovarian cancer syndrome 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1687C>T (p.Gln563X) 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. This variant was found in 5/121138 control chromosomes at a frequency of 0.0000413, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). These occurrences need to be cautiously considered due to the cohort could harbor individuals with a BRCA1 phenotype. This variant has been reported in multiple HBOC patients and multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Mendelics RCV000047559 SCV000839281 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763006 SCV000893451 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770747 SCV000902230 pathogenic Breast and/or ovarian cancer 2016-05-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000047559 SCV000966957 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-07 criteria provided, single submitter clinical testing The p.Gln563X variant in BRCA1 (also referred to as 1806C>T) has been reported i n >100 individuals with BRCA1-associated cancers (Shattuck-Eidens 1995, Wagner 1 998, Pohlreich 2003, Foretova 2004, Salazar 2006, Krajc 2008, Janav 2010, Zurade lli 2010, Blay 2013, Cunningham 2014, Kluska 2015, Cini 2016, Breast Cancer Info rmation Core (BIC) database). It was also identified in 5/66568 European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs80356898); however, this frequency is low enough to be consistent with t he frequency of hereditary breast and ovarian cancer (HBOC) in the general popul ation. This nonsense variant leads to a premature termination codon at position 563, which is predicted to lead to a truncated or absent protein. Heterozygous l oss of function of the BRCA1 gene is an established disease mechanism in HBOC. F urthermore, this variant was classified as Pathogenic on April 22, 2016 by the C linGen-approved ENIGMA expert panel (ClinVar SCV000282262.1). In summary, this v ariant meets criteria to be classified as pathogenic for HBOC in an autosomal do minant manner.
Sharing Clinical Reports Project (SCRP) RCV000031007 SCV000053600 pathogenic Breast-ovarian cancer, familial 1 2014-01-13 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031007 SCV000144157 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000031007 SCV000211992 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047559 SCV000587157 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031007 SCV000733653 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785207 SCV000923775 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000786987 SCV000925893 pathogenic Familial cancer of breast 2018-11-23 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.