ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3718C>T (p.Gln1240Ter) (rs80356903)

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Total submissions: 13
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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) RCV000077554 SCV000282316 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 RCV000048301 SCV000076314 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 1240 (p.Gln1240*). It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic. This particular variant has been reported in the literature in individuals and families with breast, ovarian, and endometrial cancer (PMID: 17645508, 24333842, 22923021, 25480878, 27393621). This variant is also known as 3837C>T in the literature. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000162866 SCV000213353 pathogenic Hereditary cancer-predisposing syndrome 2017-07-14 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)
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000048301 SCV000271317 pathogenic Hereditary breast and ovarian cancer syndrome 2015-07-29 criteria provided, single submitter clinical testing The p.Gln1240X variant in BRCA1 has been reported in 2 individuals with endometr ial cancer (Kwon 2008, Conner 2014) and at least 7 individuals with breast and/o r ovarian cancer (Novakovic 2012, Wang 2015, Breast Cancer Information Core (BIC )). It was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1240, which is predicted to lead to a truncated or absent protein. Heterozygous loss of BRCA1 function is an establish ed disease mechanism in hereditary breast and ovarian cancer (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for HBOC in an a utosomal dominant manner (http://www.partners.org/personalizedmedicine/LMM) base d upon the predicted impact to the protein, presence in affected individuals, an d absence in controls.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077554 SCV000325732 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000519156 SCV000617451 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3718C>T at the cDNA level and p.Gln1240Ter (Q1240X) at the proteinlevel. 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, previously reported as BRCA1 3837C>T using alternate nomenclature, has beenreported in several individuals with a personal and family history of breast and/or ovarian cancer (Balleine 2010,Novakovic 2012, Wang 2015). We consider this variant to be pathogenic
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077554 SCV000743403 pathogenic Breast-ovarian cancer, familial 1 2017-07-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000519156 SCV000887677 pathogenic not provided 2017-10-04 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000077554 SCV000993553 pathogenic Breast-ovarian cancer, familial 1 2019-01-22 criteria provided, single submitter research
Sharing Clinical Reports Project (SCRP) RCV000077554 SCV000109355 pathogenic Breast-ovarian cancer, familial 1 2010-06-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077554 SCV000144849 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 RCV000048301 SCV000587338 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077554 SCV000733621 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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