Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003596000 | SCV004293047 | pathogenic | Primary pulmonary hypertension | 2023-12-21 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 117 of the BMPR2 protein (p.Cys117Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with pulmonary hypertension (PMID: 18356561, 30578397, 33066286). ClinVar contains an entry for this variant (Variation ID: 425767). 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 BMPR2 protein function with a positive predictive value of 80%. This variant disrupts the p.Cys117 amino acid residue in BMPR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10973254, 12045205, 25688877, 31727138). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Rare Disease Genomics Group, |
RCV000488491 | SCV000576043 | pathogenic | Pulmonary hypertension, primary, 1 | no assertion criteria provided | literature only |