ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.890A>G (p.His297Arg) (rs139380315)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455714 SCV000538229 uncertain significance not specified 2016-04-25 criteria provided, single submitter clinical testing Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Published as VUS; ExAC: 3/11550 Latino chromosomes
Invitae RCV001246199 SCV001419539 uncertain significance Telangiectasia, hereditary hemorrhagic, type 2 2019-03-29 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 297 of the ACVRL1 protein (p.His297Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs139380315, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed to segregate with hereditary hemorrhagic telangiectasia in a family (PMID: 6470589), and has been reported in combination with another ACVRL1 variant in an individual with epistaxis (PMID: 19767588). ClinVar contains an entry for this variant (Variation ID: 161204). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
CSER _CC_NCGL, University of Washington RCV000148357 SCV000190047 uncertain significance Haemorrhagic telangiectasia 2 2014-06-01 no assertion criteria provided research

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.