ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5345G>A (p.Trp1782Ter) (rs80357219)

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Total submissions: 6
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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) RCV000112626 SCV000300245 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112626 SCV000326286 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000496911 SCV000605756 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-23 criteria provided, single submitter clinical testing The p.Trp1782X (c.5345G>A) variant in BRCA1 has been reported in at least 5 indi viduals with BRCA1-associated cancers (Evans 2003, Breast Cancer Information Cor e (BIC) database) and was absent from large population studies. In addition, a d ifferent nucleotide change (c.5346G>A) resulting in the same amino acid change ( p.Trp1782X) was reported in 15 individuals with BRCA1-associated cancers (Sobcz ak 1997; Machackova 2008; BIC database). This nonsense variant leads to a premat ure termination codon at position 1782, which is predicted to lead to a truncate d or absent protein. Heterozygous loss of function of the BRCA1 gene is an estab lished disease mechanism in hereditary breast and ovarian cancer (HBOC). In addi tion, this variant was classified as Pathogenic on September 8, 2016 by the Clin Gen-approved ENIGMA expert panel (ClinVar SCV000300245.2). In summary, the p.Trp 1782X variant meets our criteria to be classified as pathogenic for HBOC in an a utosomal dominant manner.
Ambry Genetics RCV000575788 SCV000660955 pathogenic Hereditary cancer-predisposing syndrome 2016-03-15 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)
Breast Cancer Information Core (BIC) (BRCA1) RCV000112626 SCV000145471 pathogenic Breast-ovarian cancer, familial 1 1998-06-26 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496911 SCV000587500 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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