ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.1436G>C (p.Arg479Pro) (rs1085307426)

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 RCV001241423 SCV001414437 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2019-10-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 479 of the ACVRL1 protein (p.Arg479Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hereditary hemorrhagic telangiectasia or pulmonary arterial hypertension (PMID: 20414677, 29449337, 19555857, 21158752). ClinVar contains an entry for this variant (Variation ID: 426036). 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 and their clinical significance is uncertain. This variant disrupts the p.Arg479 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16470787, 16705692, 21158752, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Medical & Molecular Genetics Group,University of Lincoln RCV000488694 SCV000576345 pathogenic Primary pulmonary hypertension 1 no assertion criteria provided literature only

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.