ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3270A>T (p.Gln1090His) (rs369925993)

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
Ambry Genetics RCV000572366 SCV000665855 uncertain significance Hereditary cancer-predisposing syndrome 2016-06-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000572366 SCV000688429 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779882 SCV000916769 uncertain significance not specified 2018-07-06 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3270A>T (p.Gln1090His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 245324 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3270A>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000466655 SCV000549424 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-03 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1090 of the BRCA1 protein (p.Gln1090His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs369925993, ExAC 0.001%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 182153). 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: "Tolerated"; 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.
Sharing Clinical Reports Project (SCRP) RCV000239193 SCV000297597 likely benign Breast-ovarian cancer, familial 1 2012-09-18 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.