Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
NIHR Bioresource Rare Diseases, |
RCV001262083 | SCV001439470 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2018-01-01 | criteria provided, single submitter | research | PM2+PM1+PP4 |
Labcorp Genetics |
RCV001262083 | SCV005734050 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 2 | 2024-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 283 of the ACVRL1 protein (p.Gly283Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 32573726; internal data). ClinVar contains an entry for this variant (Variation ID: 982489). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ACVRL1 protein function with a positive predictive value of 95%. This variant disrupts the p.Gly283 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been observed in individuals with ACVRL1-related conditions (PMID: 29743074), which suggests that this may be a clinically significant amino acid residue. 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. |