ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5212G>A (p.Gly1738Arg) (rs80356937)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112566 SCV000244392 pathogenic Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 1
Invitae RCV000239131 SCV000076876 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1738 of the BRCA1 protein (p.Gly1738Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (rs80356937, ExAC no frequency). This variant has been reported to segregate with breast and/or ovarian cancer in several families and is a founder mutation in the Greek population (PMID: 17902052, 23536787, 15353005, 24010542, 17453335, 16489001). ClinVar contains an entry for this variant (Variation ID: 55461). Experimental studies have shown that this missense variant is deleterious, as demonstrated by in vitro studies showing reduced transactivation activity as well as compromised nuclear foci formation and centrosome amplification (PMID: 17305420, 18036263, 20516115, 17308087). A different missense substitution at this codon (p.Gly1738Glu) has been determined to be pathogenic (PMID: 18465347, 23113073, 21918854, 11157798, 10811118). This suggests that the glycine residue is critical for BRCA1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
GeneKor MSA RCV000239131 SCV000296779 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112566 SCV000326218 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000112566 SCV000564322 likely pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Color RCV000579604 SCV000683272 pathogenic Hereditary cancer-predisposing syndrome 2016-08-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985433 SCV001133617 pathogenic not provided 2018-12-18 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282860 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Located in potentially important domain of the protein. Assessment of experimental evidence suggests this variant results in abnormal protein function. Appears to be associated with disease in multiple families.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112566 SCV000145396 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 RCV000239131 SCV000587480 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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.