ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.850C>T (p.Gln284Ter)

dbSNP: rs397509330
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Total submissions: 9
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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) RCV000238750 SCV000323922 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000217707 SCV000277512 pathogenic Hereditary cancer-predisposing syndrome 2021-06-16 criteria provided, single submitter clinical testing The p.Q284* pathogenic mutation (also known as c.850C>T), located in coding exon 9 of the BRCA1 gene, results from a C to T substitution at nucleotide position 850. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been reported in multiple breast and/or ovarian cancer cohorts (Seymour IJ et al. Breast Cancer Res Treat, 2008 Nov;112:343-9; Wong-Brown MW et al. Breast Cancer Res Treat, 2015 Feb;150:71-80; Shi T et al. Int J Cancer, 2017 05;140:2051-2059; Tedaldi G et al. Oncotarget, 2017 Jul;8:47064-47075; Wen WX et al. J Med Genet, 2018 02;55:97-103; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Palmero EI et al. Sci Rep, 2018 06;8:9188; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Marchetti C et al. Ann Surg Oncol, 2018 Nov;25:3701-3708; Gornjec A et al. BMC Cancer, 2019 Apr;19:296; Concolino P et al. Int J Mol Sci, 2019 Jul;20; Santonocito C et al. Cancers (Basel), 2020 May;12; Quaio CRDC et al. Am J Med Genet C Semin Med Genet, 2020 12;184:955-964). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000238750 SCV000296314 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-03-23 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000238750 SCV000326445 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000484760 SCV000568431 pathogenic not provided 2017-05-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.850C>T at the cDNA level and p.Gln284Ter (Q284X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), 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 969C>T using alternate nomenclature, has been identified in individuals with a personal and/or family history of breast and/or ovarian cancer (Seymour 2008, Wong-Brown 2015, Kwong 2016, Afghahi 2017). We consider this variant to be pathogenic.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana RCV000238750 SCV001499625 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-04-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001804784 SCV002051089 pathogenic Hereditary breast ovarian cancer syndrome 2021-12-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.850C>T (p.Gln284X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (example: c.928C>T [p.Gln310X], c.1054G>T [p.Glu352X]). The variant allele was found at a frequency of 2.8e-06 in 358032 control chromosomes. c.850C>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example: Wong-Brown_2015, Wen_2017, Santonocito_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitter has assessed this variant since 2014, including 1 expert panel and 1 consortium: all submitters have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001804784 SCV003441973 pathogenic Hereditary breast ovarian cancer syndrome 2023-09-08 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 55738). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with hereditary breast and/or ovarian cancer (PMID: 28176296, 28993434, 29446198, 30322717, 30702160). This sequence change creates a premature translational stop signal (p.Gln284*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency).
Baylor Genetics RCV000238750 SCV004216876 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2022-11-28 criteria provided, single submitter clinical testing

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