ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1831G>A (p.Val611Ile) (rs777741543)

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 RCV000165836 SCV000216583 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000165836 SCV000684160 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-20 criteria provided, single submitter clinical testing
Counsyl RCV000662932 SCV000785888 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2018-01-04 criteria provided, single submitter clinical testing
GeneDx RCV000480949 SCV000566827 uncertain significance not provided 2015-06-06 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1831G>A at the cDNA level, p.Val611Ile (V611I) at the protein level, and results in the change of a Valine to an Isoleucine (GTT>ATT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 Val611Ile was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. BRIP1 Val611Ile occurs at a position that is conserved across species and is located in the helicase domain (Cantor 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRIP1 Val611Ile is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000233742 SCV000290991 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 611 of the BRIP1 protein (p.Val611Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs777741543, ExAC 0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 186270). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.

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.