ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5485G>A (p.Glu1829Lys) (rs869320789)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Michigan Medical Genetics Laboratories,University of Michigan RCV000210967 SCV000267722 uncertain significance Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000480597 SCV000567145 uncertain significance not provided 2015-07-15 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.5485G>A at the cDNA level, p.Glu1829Lys (E1829K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAG>AAG). Using alternate nomenclature, this variant would be defined as BRCA1 5604G>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Glu1829Lys was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glutamic Acid and Lysine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Glu1829Lys occurs at a position that is not conserved and is located in the BRCT 2 domain (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether BRCA1 Glu1829Lys is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000559194 SCV000636048 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-08-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1829 of the BRCA1 protein (p.Glu1829Lys). 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 (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 225731). 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 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 and their clinical significance is uncertain. 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.
Color RCV000584194 SCV000688637 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-30 criteria provided, single submitter 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.