ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4766G>A (p.Arg1589His) (rs80357341)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048656 SCV000076669 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1589 of the BRCA1 protein (p.Arg1589His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs80357341, ExAC 0.006%). This variant has been observed in individuals with a personal or family history of breast cancer and/or ovarian cancer (PMID: 20727672, 27886673). It is also known as 4885G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 55284). Experimental studies using transcription activation assays have shown that cells carrying this variant produce results that are similar to that of cells with wild-type BRCA1 sequence (PMID: 23613828). Another study reported that this variant produces no effect on splicing by RT-PCR analysis (PMID: 21735045). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000130538 SCV000185407 likely benign Hereditary cancer-predisposing syndrome 2018-11-19 criteria provided, single submitter clinical testing In silico models in agreement (benign);Intact protein function observed in appropriate functional assay(s);Other strong data supporting benign classification
Counsyl RCV000112396 SCV000220786 likely benign Breast-ovarian cancer, familial 1 2014-10-13 criteria provided, single submitter literature only
GeneDx RCV000442424 SCV000520101 likely benign not specified 2015-10-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000130538 SCV000909012 likely benign Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing
Mendelics RCV000112396 SCV001140509 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112396 SCV000145177 uncertain significance Breast-ovarian cancer, familial 1 2007-04-10 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.