ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.190T>C (p.Cys64Arg) (rs80357064)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130787 SCV000185680 pathogenic Hereditary cancer-predisposing syndrome 2019-03-16 criteria provided, single submitter clinical testing Well-characterized mutation at same position;Good segregation with disease (lod 1.5-3 = 5-9 meioses);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Deficient protein function in appropriate functional assay(s)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083174 SCV000325176 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Color RCV000130787 SCV000688353 pathogenic Hereditary cancer-predisposing syndrome 2020-04-06 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000083174 SCV001251425 pathogenic Breast-ovarian cancer, familial 1 2019-10-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195433 SCV001365790 pathogenic Hereditary breast and ovarian cancer syndrome 2020-01-10 criteria provided, single submitter clinical testing The p.Cys64Arg variant in BRCA1 has been identified in >50 pan-ethnic individuals with BRCA1-associated cancers and segregated with disease in at least 15 individuals from several families (Caligo 1996, Willems 2009, Marchina 2010, Caleca 2014, Shi 2017, Park 2017, Rebbeck 2018, Cardoso 2018, Palmero 2018, Wen 2018, Li 2019, Deng 2019, Bhaskaran 2019, Breast Cancer Information Core (BIC; This variant has been described as a founder variant in the Italian population (Caleca 2014). In addition, it has also been reported by other clinical laboratories in ClinVar (Variation ID 54394) and was absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, and in vitro functional studies support an impact on protein function (Willems 2009, Caleca 2014, Cochran 2015, Findlay 2018). Another variant involving this codon (p.Cys64Gly) has been identified in individuals with hereditary breast and ovarian cancer (HBOC) and is currently classified as pathogenic by this laboratory. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PS4, PM2, PM5, PS3_Supporting, PP1_Strong, PP3.
Sharing Clinical Reports Project (SCRP) RCV000083174 SCV000115248 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083174 SCV000144596 uncertain significance 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 RCV000496744 SCV000587027 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Brotman Baty Institute,University of Washington RCV000083174 SCV001241646 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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