ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5179A>T (p.Lys1727Ter) (rs80357347)

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Total submissions: 11
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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) RCV000031226 SCV000300219 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048844 SCV000076857 pathogenic Hereditary breast and ovarian cancer syndrome 2020-01-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1727*) 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 observed to segregate in families affected with hereditary breast cancer (PMID: 7493024, 16287141). This variant is also known as 5298A>T in the literature. ClinVar contains an entry for this variant (Variation ID: 37645). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131827 SCV000186882 pathogenic Hereditary cancer-predisposing syndrome 2018-03-16 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Michigan Medical Genetics Laboratories,University of Michigan RCV000031226 SCV000267718 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000237069 SCV000292860 pathogenic not provided 2019-01-04 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5179A>T at the cDNA level and p.Lys1727Ter (K1727X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), 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 5298A>T using alternate nomenclature, has been reported in several families with Hereditary Breast and Ovarian Cancer (Gayther 1995, Spitzer 2000, Kroiss 2005, Hahnen 2017) and is considered pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031226 SCV000326195 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031226 SCV000489674 pathogenic Breast-ovarian cancer, familial 1 2016-11-03 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031226 SCV000053826 pathogenic Breast-ovarian cancer, familial 1 2012-05-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031226 SCV000145374 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 RCV000048844 SCV000587474 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Brotman Baty Institute,University of Washington RCV000031226 SCV001241826 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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