ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5438T>C (p.Leu1813Pro) (rs398122532)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160090 SCV000210355 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.5438T>C at the cDNA level, p.Leu1813Pro (L1813P) at the protein level, and results in the change of a Leucine to a Proline (CTT>CCT). Using alternate nomenclature, this variant would be defined as BRCA2 5666T>C. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Leu1813Pro was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Leucine and Proline differ in some properties, this is considered a semi-conservative amino acid substitution. BRCA2 Leu1813Pro occurs at a position that is not conserved and is located in the RAD51 binding domain (Roy 2012). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Leu1813Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000810148 SCV000950338 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-10-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1813 of the BRCA2 protein (p.Leu1813Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. 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: 91414). 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 proline 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) RCV000076931 SCV000108728 uncertain significance Breast-ovarian cancer, familial 2 2010-03-16 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.