ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.398G>A (p.Arg133His) (rs80357357)

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
Ambry Genetics RCV000128888 SCV000172747 likely benign Hereditary cancer-predisposing syndrome 2017-01-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification
GeneDx RCV000443460 SCV000517330 likely benign not specified 2016-10-21 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000443460 SCV000591263 uncertain significance not specified 2014-08-20 criteria provided, single submitter clinical testing
Color RCV000128888 SCV000909412 likely benign Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000443460 SCV000916766 uncertain significance not specified 2018-06-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.398G>A (p.Arg133His) results in a non-conservative amino acid change in the encoded protein sequence. Three 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 246244 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.398G>A has been reported in the literature, without strong evidence for causality. These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A functional study reporting two DNA repair assays showed the variant to have proficient activity (Towler_2013). Two 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as a VUS - possibly benign variant.
Mendelics RCV000031138 SCV001140637 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031138 SCV000053737 likely benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031138 SCV000145279 uncertain significance Breast-ovarian cancer, familial 1 1999-06-22 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.