ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.1279A>G (p.Met427Val)

gnomAD frequency: 0.00001  dbSNP: rs747090661
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 RCV001010714 SCV001170949 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-05 criteria provided, single submitter clinical testing The p.M427V variant (also known as c.1279A>G), located in coding exon 9 of the BMPR1A gene, results from an A to G substitution at nucleotide position 1279. The methionine at codon 427 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001343411 SCV001537389 uncertain significance Juvenile polyposis syndrome 2020-02-25 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 427 of the BMPR1A protein (p.Met427Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs747090661, ExAC 0.02%). This variant has not been reported in the literature in individuals with BMPR1A-related conditions. 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. 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.
All of Us Research Program, National Institutes of Health RCV001343411 SCV004837595 uncertain significance Juvenile polyposis syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 427 of the BMPR1A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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.