ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.509G>A (p.Arg170Gln) (rs80357264)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001089404 SCV000076807 likely benign Hereditary breast and ovarian cancer syndrome 2020-10-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130039 SCV000184865 likely benign Hereditary cancer-predisposing syndrome 2020-08-11 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other strong data supporting benign classification
GeneDx RCV000656995 SCV000565744 uncertain significance not provided 2018-05-03 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.509G>A at the cDNA level, p.Arg170Gln (R170Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). Using alternate nomenclature, this variant would be defined as/ has been previously published as BRCA1 628G>A. This variant has been observed in several individuals with a personal and/or family history of breast/ovarian cancer (Meindl 2002, Borg 2010, Kraus 2017). Functional assays have shown BRCA1 Arg170Gln to have functional homology directed recombination but partially defective single-strand annealing (SSA) functionality (Towler 2013). BRCA1 Arg170Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the BRD7 bindig domain . In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA1 Arg170Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000487016 SCV000605902 uncertain significance not specified 2017-06-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130039 SCV000909408 likely benign Hereditary cancer-predisposing syndrome 2018-05-25 criteria provided, single submitter clinical testing
Mendelics RCV000112724 SCV001140633 uncertain significance Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000487016 SCV001478759 uncertain significance not specified 2021-01-29 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.509G>A (p.Arg170Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.9e-05 in 254918 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (3.9e-05 vs 0.001), allowing no conclusion about variant significance. c.509G>A has been reported in the literature in individuals affected with colon cancer, breast cancer and/or ovarian cancer as well as in one unaffected control (Arver__2001, Meindl_2002, Arnold_2002, Borg_2010, Kraus_2016, De Falco V_2020). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. One co-occurrence with another pathogenic variant has been reported (BRCA2 c.67+1G>A), providing supporting evidence for a benign role (De Falco V_2020). Towler_2013 reports this variant has intermediate activity for single-strand annealing and fully functional for homology-directed recombination activity. Six ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=3) and likely benign (n=3). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112724 SCV000145604 uncertain significance Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000112724 SCV000297619 benign Breast-ovarian cancer, familial 1 2011-02-11 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.