ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.34C>T (p.Gln12Ter) (rs80357134)

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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) RCV000111614 SCV000282309 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000412855 SCV000296454 pathogenic not provided 2016-04-15 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111614 SCV000325672 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000412855 SCV000490432 pathogenic not provided 2016-07-21 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.34C>T at the cDNA level and p.Gln12Ter (Q12X) at the protein level. Using alternate nomenclature, this variant has been previously published as BRCA1 153C>T. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with hereditary breast and/or ovarian cancer (Adem 2003, Hermsen 2006, Cunningham 2014, Kwong 2016) and is considered pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000111614 SCV000575711 pathogenic Breast-ovarian cancer, familial 1 2015-09-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496757 SCV000699039 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.34C>T (p.Gln12X) 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.101delC [Pro34fsX16]). One in silico tool predicts a damaging outcome for this variant (Mutation Taster); other in silico tools were not tested since this is a LoF variant. This variant was found in 1/120998 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111614 SCV000144090 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496757 SCV000587001 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785196 SCV000923764 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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