ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5251C>T (p.Arg1751Ter) (rs80357123)

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Total submissions: 24
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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 RCV000414226 SCV000492472 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000162884 SCV000213371 pathogenic Hereditary cancer-predisposing syndrome 2017-10-25 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)
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000786961 SCV000925866 pathogenic Familial cancer of breast 2018-10-17 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077611 SCV000145411 not provided Breast-ovarian cancer, familial 1 no assertion provided clinical testing
Color RCV000162884 SCV000683276 pathogenic Hereditary cancer-predisposing syndrome 2016-03-30 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077611 SCV000326226 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077611 SCV000488332 pathogenic Breast-ovarian cancer, familial 1 2016-03-02 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077611 SCV000744590 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000077611 SCV000564307 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048882 SCV000591597 pathogenic Hereditary breast and ovarian cancer syndrome 2012-08-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077611 SCV000733592 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000077611 SCV000212009 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077611 SCV000282340 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Fulgent Genetics,Fulgent Genetics RCV000763399 SCV000894125 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
GeneDx RCV000074600 SCV000108685 pathogenic not provided 2018-12-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.5251C>T at the cDNA level and p.Arg1751Ter (R1751X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also reported as BRCA1 5370C>T using alternate nomenclature, has been reported in association with hereditary breast and ovarian cancer syndrome (Vehmanen 1997, Sarantaus 2001, Stavropoulou 2013, Churpek 2015, Alemar 2016, Pritchard 2016) and is considered pathogenic.
GeneKor MSA RCV000048882 SCV000296780 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077611 SCV000743375 pathogenic Breast-ovarian cancer, familial 1 2017-07-28 criteria provided, single submitter clinical testing
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000077611 SCV000839894 pathogenic Breast-ovarian cancer, familial 1 2017-05-25 criteria provided, single submitter clinical testing The c.5251C>T (p.Arg1751*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 9361038, 21324516, referred as c.5370C>T] and prostate cancer [PMID 27433846]. This variant creates a premature stop codon at amino acid position 1751 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant thus classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000048882 SCV000699227 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-18 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5251C>T (p.Arg1751X) 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.5266dupC (p.Glh1756fsX74), c.5289delG (p.Leu1764X), and c.5335delC (p.Gln1779fsX14)). The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple databases/clinical diagnostic laboratories cite the variant as "Pathogenic/Causal." Therefore, the variant of interest has been classified as Pathogenic.
Invitae RCV000048882 SCV000076895 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1751*) 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 multiple individuals with breast and ovarian cancer (PMID: 9361038, 21324516, 24010542, 21232165, 25428789), and an individual with prostate cancer (PMID: 27433846). This variant is also known as 5370C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 55480). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000048882 SCV000605749 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-28 criteria provided, single submitter clinical testing The p.Arg1751X variant in BRCA1 has been identified in >50 individuals with BRCA 1-associated cancers (Konstantopoulou 2014, Stegal 2011, Stavropoulou 2013, Brea st Cancer Information Core (BIC) database) and was absent from large population studies. This nonsense variant leads to a premature termination codon at positio n 1751, which is predicted to lead to a truncated or absent protein. Heterozygou s loss of function of the BRCA1 gene is an established disease mechanism in here ditary breast and ovarian cancer (HBOC). Furthermore, this variant was classifie d as Pathogenic on Apr 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (Cli nVar SCV000282340.1). In summary, this variant meets our criteria to be classifi ed as pathogenic for HBOC in an autosomal dominant manner.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074600 SCV000296322 pathogenic not provided 2015-04-03 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048882 SCV000587482 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077611 SCV000109414 pathogenic Breast-ovarian cancer, familial 1 2013-09-16 no assertion criteria provided clinical testing

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