ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.772G>A (p.Gly258Ser) (rs1555152966)

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 RCV000694605 SCV000823056 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2020-04-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 258 of the ACVRL1 protein (p.Gly258Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 6 of the ACVRL1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 31220907, 20414677, Invitae). ClinVar contains an entry for this variant (Variation ID: 444101). 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). For these reasons, this variant has been classified as Pathogenic.
Genetics,Medical University of Vienna RCV000513504 SCV000346041 likely pathogenic Hereditary hemorrhagic telangiectasia type 1 no assertion criteria provided clinical testing

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.