ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.2338C>T (p.Gln780Ter) (rs80356945)

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Total submissions: 19
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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) RCV000077515 SCV000282277 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 RCV000047805 SCV000075818 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln780*) 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 individuals and families affected with breast and/or ovarian cancer (PMID: 7663517, 9667259, 16683254, 21324516, 22006311, 22752604). It is also known as 2457C>T, Q780X in the literature. ClinVar contains an entry for this variant (Variation ID: 54540). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000077515 SCV000154010 pathogenic Breast-ovarian cancer, familial 1 2014-01-10 criteria provided, single submitter literature only
Ambry Genetics RCV000162854 SCV000213341 pathogenic Hereditary cancer-predisposing syndrome 2018-01-15 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)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000414114 SCV000296375 pathogenic not provided 2015-08-14 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077515 SCV000325327 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000414114 SCV000490433 pathogenic not provided 2018-06-07 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2338C>T at the cDNA level and p.Gln780Ter (Q780X) 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 published as BRCA1 2457C>T using alternate nomenclature, has been reported in association with breast and/or ovarian cancer (Friedman 1995, Peelen 1997, Frank 1998, Walsh 2011, Weren 2016) and is considered pathogenic.
Department of Pathology and Molecular Medicine,Queen's University RCV000047805 SCV000588039 pathogenic Hereditary breast and ovarian cancer syndrome 2017-04-20 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000047805 SCV000591380 pathogenic Hereditary breast and ovarian cancer syndrome criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000047805 SCV000605748 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-28 criteria provided, single submitter clinical testing The p.Gln780X variant in BRCA1 has been reported in >30 individuals with BRCA1-a ssociated cancers (Hogervorst 1995, Frank 1998, Meindl 2002, van der Hout 2006, Walsh 2011, Zhang 2011, Juwle 2012, Breast Cancer Information Core (BIC) databas e). This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 780, which is predicted to l ead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in individuals with hereditary breast and ovarian cancer (HBOC). In addition, this variant was classified as Pathogeni c on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV0002 82277.1). In summary, this variant meets our criteria to be classified as pathog enic for HBOC in an autosomal dominant manner.
Color RCV000162854 SCV000683028 pathogenic Hereditary cancer-predisposing syndrome 2014-12-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000047805 SCV000698940 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-03 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2338C>T (p.Gln780X) 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.2389G>T/p.Glu797X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121352 control chromosomes. This variant has been reported in many HBOC patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000077515 SCV000743417 pathogenic Breast-ovarian cancer, familial 1 2014-10-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077515 SCV000744661 pathogenic Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077515 SCV000109315 pathogenic Breast-ovarian cancer, familial 1 2012-10-15 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077515 SCV000144385 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 RCV000047805 SCV000587206 pathogenic Hereditary breast and ovarian cancer syndrome 2015-01-22 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077515 SCV000733644 pathogenic Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785402 SCV000923974 pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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