ClinVar Miner

Submissions for variant NM_000020.3(ACVRL1):c.1189G>A (p.Asp397Asn)

dbSNP: rs1940836783
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 RCV001056963 SCV001221430 pathogenic Telangiectasia, hereditary hemorrhagic, type 2 2023-08-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 397 of the ACVRL1 protein (p.Asp397Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary hemorrhagic telangiectasia (PMID: 15517393, 16690726; Invitae). ClinVar contains an entry for this variant (Variation ID: 852370). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACVRL1 protein function. This variant disrupts the p.Asp397 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 15024723; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002339285 SCV002641727 pathogenic Cardiovascular phenotype 2015-02-10 criteria provided, single submitter clinical testing The p.D397N pathogenic mutation (also known as c.1189G>A), located in coding exon 7 of the ACVRL1 gene, results from a G to A substitution at nucleotide position 1189. The aspartic acid at codon 397 is replaced by asparagine, an amino acid with highly similar properties. This mutation was reported in a Dutch individual with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) (Letteboer TG et al. Hum. Genet., 2005 Jan;116:8-16). Based on the supporting evidence, p.D397N is interpreted as a disease-causing mutation.

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.