ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1340C>T (p.Pro447Leu) (rs587776459)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000509642 SCV000607923 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000509642 SCV000908527 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-20 criteria provided, single submitter clinical testing
Counsyl RCV000144180 SCV000488034 uncertain significance Breast-ovarian cancer, familial 2 2015-12-16 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000502802 SCV000593760 uncertain significance not specified 2017-03-15 criteria provided, single submitter clinical testing
Invitae RCV000795705 SCV000935175 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-09-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 447 of the BRCA2 protein (p.Pro447Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 156163). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The leucine amino acid residue is 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 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.
Sharing Clinical Reports Project (SCRP) RCV000144180 SCV000189253 uncertain significance Breast-ovarian cancer, familial 2 2009-05-19 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.