ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1141C>G (p.Leu381Val) (rs864622566)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206145 SCV000261134 uncertain significance Juvenile polyposis syndrome 2015-10-13 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 381 of the BMPR1A protein (p.Leu381Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual with suspected Lynch syndrome (PMID: 25980754). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this is a rare missense change that has been found in an affected individual and is predicted to alter protein function. In the absence of further supportive evidence, this variant has been classified as a Variant of Uncertain Significance.
GeneDx RCV000478590 SCV000567456 uncertain significance not provided 2015-07-27 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.1141C>G at the cDNA level, p.Leu381Val (L381V) at the protein level, and results in the change of a Leucine to a Valine (CTG>GTG). This variant was observed in an individual with suspected Lynch syndrome (Yurgelun 2015). BMPR1A Leu381Val 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 Leucine and Valine share similar properties, this is considered a conservative amino acid substitution. BMPR1A Leu381Val occurs at a position that is conserved across species and is located within the protein domain (Howe 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BMPR1A Leu381Val is pathogenic or benign. We consider it to be 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.