ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4183C>T (p.Gln1395Ter) (rs80357260)

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Total submissions: 17
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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 RCV000778172 SCV000914330 pathogenic Familial cancer of breast 2019-01-30 criteria provided, single submitter research
Ambry Genetics RCV000162874 SCV000213361 pathogenic Hereditary cancer-predisposing syndrome 2017-12-07 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) RCV000077564 SCV000145005 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162874 SCV000683156 pathogenic Hereditary cancer-predisposing syndrome 2015-02-24 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077564 SCV000325875 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077564 SCV000220260 likely pathogenic Breast-ovarian cancer, familial 1 2014-04-21 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496276 SCV000591497 pathogenic Hereditary breast and ovarian cancer syndrome 2013-02-26 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077564 SCV000733613 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000077564 SCV000212002 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) RCV000077564 SCV000282324 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 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 RCV000735467 SCV000863604 pathogenic Breast and/or ovarian cancer 2013-08-09 no assertion criteria provided clinical testing
GeneDx RCV000212181 SCV000210169 pathogenic not provided 2018-04-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.4183C>T at the cDNA level and p.Gln1395Ter (Q1395X) at the protein level. This variant is also known as BRCA1 4302C>T using alternate nomenclature. The substitution creates a nonsense variant, changing 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. BRCA1 Gln1395Ter has been reported in several individuals with early-onset and/or familial breast or ovarian cancer and is reported to be a pathogenic founder variant in the Tyrol region of Austria (Langston 1996, Sensi 2003, Rashid 2006, Singer 2014, Polsler 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496276 SCV000699114 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-11 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4183C>T (p.Gln1395X) variant causes a nonsense mutation in exon 9 resulting in a premature termination codon, a known mechanism for disease, as these types of variants are predicted to cause transcript degradation through nonsense mediated decay or produce a truncated protein. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), but has been reported in multiple affected individuals via publications. In addition, multiple reputable databases/clinical laboratories cite the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic.
Mendelics RCV000496276 SCV000839239 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212181 SCV000296397 pathogenic not provided 2015-10-14 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496276 SCV000587380 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077564 SCV000109366 pathogenic Breast-ovarian cancer, familial 1 2012-09-17 no assertion criteria provided clinical testing

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