Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001039935 | SCV001203485 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 2 | 2020-03-18 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Pro378 amino acid residue in ACVRL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20414677, 26176610, 21158752, 24196379, 15712271). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 has been observed in an individual with clinical features of hereditary hemorrhagic telangiectasia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with arginine at codon 378 of the ACVRL1 protein (p.Pro378Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. |