ClinVar Miner

Submissions for variant NM_000020.2(ACVRL1):c.406_409del (p.Gly136fs) (rs863223416)

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
GeneDx RCV000196965 SCV000249637 pathogenic not provided 2016-12-07 criteria provided, single submitter clinical testing The c.406_409delGGTG pathogenic variant in the ACVRL1 gene has been reported in association with HHT in one affected proband out of a cohort of 50 patients, and was absent from >100 healthy individuals (Klaus et al.,1998). Furthermore, the c.406_409delGGTG variant 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. This variant causes a shift in reading frame starting at codon Glycine 136, changing it to a Serine, and creating a premature stop codon at position 28 of the new reading frame, denoted p.Gly136SerfsX28. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the ACVRL1 gene have been reported in the Human Gene Mutation Database in association with HHT (Stenson et al., 2014).
Invitae RCV000694342 SCV000822782 pathogenic Hereditary hemorrhagic telangiectasia type 2 2018-04-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly136Serfs*28) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs750662466, ExAC 0.02%). This variant has been reported in an individual affected with hereditary hemorrhagic telangiectasia (HHT) (PMID: 10694922, 15879500). This variant is also described as p.G136fs in the literature. ClinVar contains an entry for this variant (Variation ID: 212806). Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). For these reasons, this variant has been classified as Pathogenic.

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.