ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1336A>C (p.Ile446Leu)

dbSNP: rs786203496
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
Ambry Genetics RCV000166825 SCV000217639 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-06 criteria provided, single submitter clinical testing The p.I446L variant (also known as c.1336A>C), located in coding exon 8 of the BRIP1 gene, results from an A to C substitution at nucleotide position 1336. The isoleucine at codon 446 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000709550 SCV000839383 uncertain significance Fanconi anemia complementation group J 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001047345 SCV001211296 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2019-11-21 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 187131). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 446 of the BRIP1 protein (p.Ile446Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine.

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.