ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5346G>A (p.Trp1782Ter) (rs80357284)

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Total submissions: 14
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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) RCV000031239 SCV000300246 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131866 SCV000186921 pathogenic Hereditary cancer-predisposing syndrome 2017-12-27 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)
Michigan Medical Genetics Laboratories,University of Michigan RCV000031239 SCV000267719 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000256177 SCV000321443 pathogenic not provided 2018-03-12 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.5346G>A at the cDNA level and p.Trp1782Ter (W1782X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, also known as 5465G>A, has been reported in association with breast and/or ovarian cancer (Sobczak 1997, Geisler 2002, Evans 2003, Perkowska 2003, Kroiss 2005, Machackova 2008, van Harssel 2010, Cybulski 2014) and is considered pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031239 SCV000326287 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031239 SCV000489335 pathogenic Breast-ovarian cancer, familial 1 2016-09-20 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000496476 SCV000605759 pathogenic Hereditary breast and ovarian cancer syndrome 2017-01-27 criteria provided, single submitter clinical testing The p.Trp1782X (c.5346G>A) variant in BRCA1 has been reported in 15 individuals with BRCA1-associated cancers (Breast cancer information core (BIC) database, Ma chackova 2008, Sobczak 1997) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1782, which is predicted to lead to a truncated or absent protein. Heterozygous loss of func tion of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Additionally, the p.Trp1782X variant was classified a s Pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA Expert Panel (S CV000300246.2). In summary, this variant meets criteria to be classified as path ogenic for HBOC in an autosomal dominant manner based upon its predicted impact to the protein, absence from controls, and multiple reports in affected individu als.
Color RCV000131866 SCV000683301 pathogenic Hereditary cancer-predisposing syndrome 2016-06-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000256177 SCV000887724 pathogenic not provided 2018-08-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031239 SCV000053843 pathogenic Breast-ovarian cancer, familial 1 2010-05-19 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031239 SCV000145472 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Division Human Genetics,Medical University Innsbruck RCV000031239 SCV000212011 pathogenic Breast-ovarian cancer, familial 1 2015-02-11 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496476 SCV000587501 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000256177 SCV000778732 pathogenic not provided 2017-01-31 no assertion criteria provided clinical testing

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