Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center For Human Genetics And Laboratory Diagnostics, |
RCV001353251 | SCV001548394 | likely pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2021-01-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001353251 | SCV004293371 | pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2023-01-20 | criteria provided, single submitter | clinical testing | This variant is also known as p.Arg169Gln. This missense change has been observed in individuals with autosomal dominant protein C deficiency (PMID: 8499565, 17152060, 28607330, 32717757). This variant is present in population databases (rs199469476, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 211 of the PROC protein (p.Arg211Gln). ClinVar contains an entry for this variant (Variation ID: 1048661). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg211Trp amino acid residue in PROC. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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 PROC protein function. |