ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.5521A>C (p.Ser1841Arg) (rs80357299)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Sharing Clinical Reports Project (SCRP) RCV000031262 SCV000053866 uncertain significance Breast-ovarian cancer, familial 1 2010-05-21 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031262 SCV000145564 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496641 SCV000587519 uncertain significance not specified 2014-01-31 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501320 SCV000591638 likely pathogenic not provided no assertion criteria provided clinical testing The BRCA1 p.Ser1841Arg variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was identified in dbSNP (rs80357299) as “with likely pathogenic allele”, ClinVar (classified as uncertain significance by BIC, SCRP and Women's College Hospital and likely pathogenic by Lady Davis Institute for Medical Research) and LOVD 3.0 (observed 1x). The variant was not identified in UMD-LSDB. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). In vitro expression of the variant had a demonstrable effect on BRCA1 protein folding, binding and transactivational activity (Lee 2010). Additionally, the variant co-segregated with disease in a family; it was identified in a patient with ovarian cancer, and segregated in 3 family members, including one prostate cancer and two breast cancer cases (Zhang 2013). The p.Ser1841 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735509 SCV000863647 likely pathogenic Breast and/or ovarian cancer no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000031262 SCV001243498 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.