Total submissions: 2
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. |