ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3555G>T (p.Glu1185Asp) (rs587779368)

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
Ambry Genetics RCV000165151 SCV000215862 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient evidence,In silico models in agreement (benign)
Color RCV000165151 SCV000688440 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000074581 SCV000591451 uncertain significance not specified 2015-05-22 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765363 SCV000896628 uncertain significance 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 RCV000766573 SCV000108666 uncertain significance not provided 2018-12-24 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.3555G>T at the cDNA level, p.Glu1185Asp (E1185D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAG>GAT). Using alternate nomenclature, this variant would be defined as BRCA1 3674G>T. This variant was observed in at least one woman with ovarian cancer (Alsop 2012). BRCA1 Glu1185Asp was not observed in large population cohorts (Lek 2016). BRCA1 Glu1185Asp is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA1 Glu1185Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000469806 SCV000549379 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 1185 of the BRCA1 protein (p.Glu1185Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (rs587779368, ExAC no frequency). This variant has been observed in an individual affected with ovarian cancer (PMID: 22711857). ClinVar contains an entry for this variant (Variation ID: 89059). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074581 SCV000600336 uncertain significance not specified 2017-05-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077551 SCV000109352 uncertain significance Breast-ovarian cancer, familial 1 2010-03-15 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.