Description
Identified in multiple heterozygous individuals with protein S deficiency and some of these individuals have a history of thrombosis (Duchemin et al., 1995; Borgel et al., 1996; Espinosa-Parrilla et al., 2000; Labrouche et al., 2003; Beauchamp et al., 2004; ten Kate et al., 2008; Suchon et al., 2017; Wypasek et al., 2017); Reported in at least one asymptomatic homozygous individual with type I protein S deficiency and protein S levels lower than heterozygous individuals (Espinosa-Parilla et al., 2000; Giri et al., 2000); Segregates with protein S deficiency in multiple relatives from unrelated families; however, it was absent from some relatives with protein S deficiency, and it has been found in relatives without protein S deficiency, as well as in unrelated control individuals (Duchemin et al., 1995; Espinosa-Parrilla et al., 1997; Beauchamp et al., 2004; ten Kate et al., 2008); Several individuals with a history of thrombotic events who harbored this variant also harbored additional variants, including factor V Leiden (Borgel et al., 1996; Espinosa-Parrilla et al., 2000; Wypasek et al., 2014; Bruwer et al., 2016); Although at least one early study found no significant difference in the frequency of this variant in individuals with thrombophilia versus controls, a subsequent larger study did find an increased frequency of this variant in individuals with venous thrombosis, with an estimated odds ratio of 6.57 (Bertina et al., 1990; Suchon et al., 2017); Published in vitro assays demonstrate that the S501P variant is associated with faster clearance than wild-type protein S (Denis et al., 2005); An additional functional study suggests that S501P displays deficient APC-cofactor activity in the degradation of factor V Leiden and that there may be synergistic effects between thrombophilic risk factors, while another study reports that S501P has no impact on APC-cofactor and APC-independent coagulation activities (Giri et al., 2000; Koenen et al., 2004); In silico analysis supports that this missense variant does not alter protein structure/function; Also described as the Heerlen allele/polymorphism or S460P using alternate nomenclature; This variant is associated with the following publications: (PMID: 9108398, 15175796, 10887114, 18841302, 24119292, 29883906, 27838551, 18435454, 24365770, 24014240, 12960605, 8765219, 20880255, 31019283, 7579448, 10669162, 28607330, 28374852, 2143091, 15147381, 16100035, 21764424, 22273984)
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
