ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1709C>A (p.Pro570Gln) (rs879254020)

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 RCV000759496 SCV000293197 uncertain significance not provided 2015-09-30 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.1709C>A at the cDNA level, p.Pro570Gln (P570Q) at the protein level, and results in the change of a Proline to a Glutamine (CCA>CAA). Using alternate nomenclature, this variant would be defined as BRCA1 1828C>A. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA1 Pro570Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Proline and Glutamine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 Pro570Gln occurs at a position that is not conserved and is located in the DNA binding domain and in a region known to interact with multiple other proteins (Narod 2004, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA1 Pro570Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000238872 SCV000296372 uncertain significance Breast-ovarian cancer, familial 1 2016-05-05 criteria provided, single submitter clinical testing
Invitae RCV000524967 SCV000635809 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-22 criteria provided, single submitter clinical testing This sequence change replaces proline with glutamine at codon 570 of the BRCA1 protein (p.Pro570Gln). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and glutamine. 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: 245965). 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 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759496 SCV000888845 uncertain significance not provided 2017-12-14 criteria provided, single submitter clinical testing
Color RCV000771381 SCV000903705 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-30 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.