Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000645700 | SCV000767451 | likely pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2023-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 183 of the PROC protein (p.Cys183Phe). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects PROC function (PMID: 22627591). 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. ClinVar contains an entry for this variant (Variation ID: 536969). This variant is also known as Cys141Phe. This missense change has been observed in individuals with protein C deficiency (PMID: 22627591; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.0009%). |
| Illumina Laboratory Services, |
RCV000645700 | SCV002540241 | uncertain significance | Thrombophilia due to protein C deficiency, autosomal dominant | 2022-02-01 | criteria provided, single submitter | clinical testing | The PROC c.548G>T (p.Cys183Phe) missense variant results in the substitution of cysteine at amino acid position 183 with phenylalanine. This variant has been reported in a heterozygous state in one individual with protein C deficiency with a measured protein C activity of 51% of normal (Caspers et al. 2012). The c.548G>T variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000009 in the European (non-Finnish) population (version 2.1.1). Based on the available evidence, the c.548G>T (p.Cys183Phe) variant is classified as a variant of uncertain significance for protein C deficiency. |