ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3410T>C (p.Met1137Thr) (rs80357297)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048182 SCV000076195 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-12-15 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 1137 of the BRCA1 protein (p.Met1137Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (rs80357297, ExAC no frequency). This variant has been reported in an individual affected with breast cancer and an individual with high risk of breast and/or ovarian cancer (PMID: 19491284, 22476429). ClinVar contains an entry for this variant (Variation ID: 54871). 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 threonine amino acid residue is also 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. 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.
GeneDx RCV000212173 SCV000209952 likely benign not specified 2014-03-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000509877 SCV000607976 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000112089 SCV000785738 uncertain significance Breast-ovarian cancer, familial 1 2017-11-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759520 SCV000888890 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Color RCV000509877 SCV000909304 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212173 SCV000918731 uncertain significance not specified 2018-04-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3410T>C (p.Met1137Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 245894 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.3410T>C, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Lu_2012, Haffty_2009). These reports do not provide unequivocal conclusions about an association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112089 SCV000144755 uncertain significance Breast-ovarian cancer, familial 1 1997-11-14 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.