ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2998G>A (p.Glu1000Lys) (rs80357124)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048034 SCV000076047 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1000 of the BRCA1 protein (p.Glu1000Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (rs80357124, ExAC no frequency). This variant has been reported in the literature as part of a BRCA1 mutation screening (PMID: 16267036) and in an individual with breast cancer in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 54742). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The lysine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000131313 SCV000186286 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-06 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000111977 SCV000144602 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 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.