ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.131G>T (p.Cys44Phe) (rs80357446)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166901 SCV000217719 pathogenic Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Deficient protein function in appropriate functional assay(s),Other strong data supporting pathogenic classification,Structural Evidence,Well-characterized mutation at same position
Breast Cancer Information Core (BIC) (BRCA1) RCV000077487 SCV000144404 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Color RCV000166901 SCV000682947 pathogenic Hereditary cancer-predisposing syndrome 2016-11-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077487 SCV000325012 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000077487 SCV000677632 pathogenic Breast-ovarian cancer, familial 1 2017-02-01 criteria provided, single submitter clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735465 SCV000863602 pathogenic Breast and/or ovarian cancer 2011-11-10 no assertion criteria provided clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763011 SCV000893456 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000434130 SCV000512277 pathogenic not provided 2018-04-18 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.131G>T at the cDNA level, p.Cys44Phe (C44F) at the protein level, and results in the change of a Cysteine to a Phenylalanine (TGC>TTC). This variant, also reported as 250G>T using alternate nomenclature, has been identified in several individuals with personal and/or family histories consistent with Hereditary Breast and Ovarian Cancer syndrome (John 2007, Hall 2009, Jalkh 2012, Lolas Hamameh 2017). Functional analyses have found BRCA1 Cys44Phe to disrupt homology-directed repair and BARD1 binding, as well as result in loss of E3 ubiquitin ligase activity and centrosome amplification (Morris 2006, Ransburgh 2010, Kais 2012, Starita 2015). BRCA1 Cys44Phe was not observed in large population cohorts (Lek 2016). This variant is located in the BRD7 and BARD1 binding domains and at a ubiquitination site within the RING finger domain (Wu 1996, Narod 2004, Borg 2010, Harte 2010, Paul 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on the current evidence, we consider this variant to be pathogenic.
GeneKor MSA RCV000434130 SCV000296760 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000496386 SCV000918696 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-07 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.131G>T (p.Cys44Phe) results in a non-conservative amino acid change located in the RING binding domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 245760 control chromosomes (gnomAD). The variant, c.131G>T, has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Alsop_2012, Jalkh_2012, El Saghir_2015, Christie_2017, etc). These data indicate that the variant is very likely to be associated with disease. Multiple functional studies found that the variant significantly impacts proper BRCA1 protein function (Kais_2012, Morris_2006,Ransburgh_2010, Towler_2013, and Thouvenot_2016). Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely pathogenic/pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000077487 SCV000267678 pathogenic Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077487 SCV000296342 pathogenic Breast-ovarian cancer, familial 1 2015-05-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000434130 SCV000888841 pathogenic not provided 2015-05-14 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496386 SCV000587017 likely pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-17 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077487 SCV000109285 pathogenic Breast-ovarian cancer, familial 1 2012-08-07 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.