ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1760A>T (p.His587Leu) (rs876660646)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216569 SCV000278250 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Counsyl RCV000662901 SCV000785822 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-12-12 criteria provided, single submitter clinical testing
GeneDx RCV000219246 SCV000279642 uncertain significance not provided 2017-11-13 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1760A>T at the cDNA level, p.His587Leu (H587L) at the protein level, and results in the change of a Histidine to a Leucine (CAT>CTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRIP1 His587Leu was not observed in large population cohorts (Lek 2016). Since Histidine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRIP1 is not located in a known functional domain. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether BRIP1 His587Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000460900 SCV000547349 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-09-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with leucine at codon 587 of the BRIP1 protein (p.His587Leu). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 233799). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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.