ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2401T>C (p.Cys801Arg) (rs1064793591)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479023 SCV000566540 uncertain significance not provided 2017-03-29 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.2401T>C at the cDNA level, p.Cys801Arg (C801R) at the protein level, and results in the change of a Cysteine to an Arginine (TGT>CGT). Using alternate nomenclature, this variant would be defined as BRCA1 2520T>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Cys801Arg was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Cysteine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Cys801Arg occurs at a position that is not conserved and is located in the DNA-binding domain and a region known to interact with multiple other proteins (Narod 2004, Paul 2004). Protein based in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function and splicing models predict the creation of a cryptic splice donor site, upstream of the natural splice donor site. Based on currently available evidence, it is unclear whether BRCA1 Cys801Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000794192 SCV000933586 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 801 of the BRCA1 protein (p.Cys801Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 17922257). This variant is also known as 2460 T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 419022). 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 arginine 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.

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.