ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5213G>A (p.Gly1738Glu) (rs80357450)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048864 SCV000076877 pathogenic Hereditary breast and ovarian cancer syndrome 2016-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 1738 of the BRCA1 protein (p.Gly1738Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals and families affected with breast cancer and ovarian cancer (PMID: 18465347, 23113073, 21918854). Experimental studies have shown that this missense change impairs the stability and transcription activity of the BRCA2 protein (PMID: 11157798, 20516115, 10811118). A different missense substitution at this codon (p.Gly1738Arg) has been reported to be deleterious (PMID: 21990134). This indicates that the glycine residue is important for BRCA1 protein function. For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077609 SCV000326221 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000077609 SCV000564324 likely pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV001190130 SCV001357548 pathogenic Hereditary cancer-predisposing syndrome 2018-12-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000048864 SCV001363823 pathogenic Hereditary breast and ovarian cancer syndrome 2019-08-23 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5213G>A (p.Gly1738Glu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251492 control chromosomes (gnomAD). c.5213G>A has been reported in the literature in several individuals and families affected with Hereditary Breast and Ovarian Cancer (Keshavarzi_2012, Nielsen_2016). These data indicate that the variant is very likely to be associated with disease. Multiple publications reported experimental evidence evaluating an impact on protein function, and demonstrated protein folding defect, compromised phosphopeptide binding, and decreased transcriptional activity in yeast and human cells (Hayes_2000, Lee_2010). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and they classified the variant as pathogenic (2x) / likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077609 SCV000109412 likely pathogenic Breast-ovarian cancer, familial 1 2012-08-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077609 SCV000145397 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000077609 SCV001237929 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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.