ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.60A>C (p.Lys20Asn) (rs202168814)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159933 SCV000210065 uncertain significance not provided 2017-12-04 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.60A>C at the cDNA level, p.Lys20Asn (K20N) at the protein level, and results in the change of a Lysine to an Asparagine (AAA>AAC). This variant, also denoted as 179A>C using alternate numbering, has been reported in the literature as a variant of uncertain significance in an individual with a personal history of early-onset breast cancer and a family history of breast cancer and in an individual referred for multi-gene hereditary cancer testing (Lara 2012, Mu 2016). BRCA1 Lys20Asn was not observed at a significant frequency in large population cohorts (Lek 2016). Since Lysine and Asparagine differ in some properties, this is considered a semi-conservative amino acid substitution and may affect protein integrity. BRCA1 Lys20Asn is located in the RING domain and a region known to interact with BRD7 and BARD1 (Narod 2004, Borg 2010, Harte 2010, Paul 2014). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on currently available information, it is unclear whether BRCA1 Lys20Asn is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000215880 SCV000275654 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-08 criteria provided, single submitter clinical testing
Invitae RCV000549303 SCV000636064 uncertain significance Hereditary breast and ovarian cancer syndrome 2017-08-25 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 20 of the BRCA1 protein (p.Lys20Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (rs202168814, ExAC no frequency). This variant has been reported in an individual affected with early-onset breast cancer (PMID: 23096355). ClinVar contains an entry for this variant (Variation ID: 182121). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000549303 SCV000839319 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159933 SCV000888958 uncertain significance not provided 2018-06-22 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.