ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.182G>A (p.Cys61Tyr) (rs80357093)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235674 SCV000293061 pathogenic not provided 2016-05-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.182G>A at the cDNA level, p.Cys61Tyr (C61Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT) This variant, previously published as BRCA1 301G>A using alternate nomenclature, has been observed in several individuals with a personal/family history of breast cancer and has been described as a recurrent pathogenic variant in the African-American population (John 2007, Churpek 2015, Pal 2015). Another non-conservative missense variant affecting the same residue, BRCA1 Cys61Gly, is recurrent in Central and Eastern European populations and has been classified as disease-causing based on multifactorial likelihood analysis as well as in vivo and in vitro functional assays (Morris 2006, Janavicius 2010, Lindor 2012, Bouwman 2013). BRCA1 Cys61Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Cysteine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys61Tyr occurs at a position that is conserved in mammals and is located in the RING-type Zinc finger domain (Borg 2010). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the current evidence, we consider this variant to be pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077497 SCV000325156 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496241 SCV000591247 pathogenic Hereditary breast and ovarian cancer syndrome 2014-04-17 criteria provided, single submitter clinical testing
Color RCV000775191 SCV000909417 pathogenic Hereditary cancer-predisposing syndrome 2017-08-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775191 SCV001173919 likely pathogenic Hereditary cancer-predisposing syndrome 2019-08-13 criteria provided, single submitter clinical testing Deficient protein function in appropriate functional assay(s);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Structural Evidence;Well-characterized mutation at same position
Sharing Clinical Reports Project (SCRP) RCV000077497 SCV000109296 pathogenic Breast-ovarian cancer, familial 1 2011-05-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077497 SCV000144576 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 RCV000496241 SCV000587025 pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-17 no assertion criteria provided research
Brotman Baty Institute,University of Washington RCV000077497 SCV001242517 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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