Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV001262085 | SCV001439474 | likely benign | Telangiectasia, hereditary hemorrhagic, type 2 | 2018-01-01 | criteria provided, single submitter | research | BS1 +BP2 |
Invitae | RCV001262085 | SCV002300654 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 2 | 2022-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 316 of the ACVRL1 protein (p.Glu316Asp). This variant is present in population databases (rs145300204, gnomAD 0.01%). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia and/or pulmonary arterial hypertension (PMID: 32573726; Invitae). ClinVar contains an entry for this variant (Variation ID: 982491). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |