Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000645701 | SCV000767452 | pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 271 of the PROC protein (p.Arg271Trp). This variant is present in population databases (rs767112991, gnomAD 0.003%). This missense change has been observed in individuals with protein C deficiency (PMID: 7482420, 18954896, 28111891; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 536970). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PROC function (PMID: 27172833). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002269295 | SCV002552720 | likely pathogenic | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | Identified in the heterozygous state in patients with deep vein thrombosis or symptomatic protein C deficiency in published literature (Miyata et al., 2009; Martos et al., 2019); Published functional studies demonstrate a severe reduction in the rate of protein C activation by thrombin-thrombomodulin (Alsultan et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported as p.(R229W) using alternate nomenclature in some cases; This variant is associated with the following publications: (PMID: 27172833, 18954896, 28111891, 7482420, 31254973, 30487363) |
ISTH- |
RCV000645701 | SCV002569210 | uncertain significance | Thrombophilia due to protein C deficiency, autosomal dominant | criteria provided, single submitter | clinical testing | ||
Fulgent Genetics, |
RCV002507104 | SCV002813271 | pathogenic | Thrombophilia due to protein C deficiency, autosomal recessive; Thrombophilia due to protein C deficiency, autosomal dominant | 2021-10-20 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000645701 | SCV004805014 | likely pathogenic | Thrombophilia due to protein C deficiency, autosomal dominant | 2024-03-17 | criteria provided, single submitter | research |