Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378884 | SCV001576572 | likely pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2024-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 367 of the PROC protein (p.Val367Met). This variant is present in population databases (rs140582220, gnomAD 0.0009%). This missense change has been observed in individuals with clinical features of protein C deficiency (PMID: 10669160, 22627591, 27995882, 28174134, 34650936). This variant is also known as Val325Met, V325M, and G15240A. ClinVar contains an entry for this variant (Variation ID: 1067579). 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 not expected to disrupt PROC protein function with a negative predictive value of 80%. This variant disrupts the p.Val367 amino acid residue in PROC. Other variant(s) that disrupt this residue have been observed in individuals with PROC-related conditions (PMID: 7841324, 35026611), which suggests that this may be a clinically significant amino acid residue. 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. |