Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000817776 | SCV000958359 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2023-03-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 660559). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 229 of the ACVRL1 protein (p.Lys229Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hereditary hemorrhagic telangiectasia (Invitae). 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.Lys229 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 16429404, 16690726; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |