ClinVar Genomic variation as it relates to human health
NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Likely pathogenic(1); Uncertain significance(6); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro)
Variation ID: 13316 Accession: VCV000013316.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3q11.1 3: 93879306 (GRCh38) [ NCBI UCSC ] 3: 93598150 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Jan 6, 2024 Oct 27, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000313.4:c.1501T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000304.2:p.Ser501Pro missense NM_001314077.2:c.1597T>C NP_001301006.1:p.Ser533Pro missense NC_000003.12:g.93879306A>G NC_000003.11:g.93598150A>G NG_009813.1:g.99785T>C LRG_572:g.99785T>C LRG_572t1:c.1501T>C LRG_572p1:p.Ser501Pro P07225:p.Ser501Pro - Protein change
- S501P, S533P
- Other names
- S460P
- Canonical SPDI
- NC_000003.12:93879305:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00100 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00100
1000 Genomes Project 30x 0.00125
Trans-Omics for Precision Medicine (TOPMed) 0.00254
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PROS1 | - | - |
GRCh38 GRCh37 |
475 | 504 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Feb 4, 2019 | RCV000246742.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 27, 2022 | RCV000205145.5 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Nov 21, 2018 | RCV000755688.10 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jul 12, 2022 | RCV001358591.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 15, 2021 | RCV003447474.1 | |
Protein S Heerlen
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Pathogenic (1) |
no assertion criteria provided
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Jun 1, 2004 | RCV000014244.17 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 21, 2018)
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criteria provided, single submitter
Method: clinical testing
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Thrombophilia due to protein S deficiency, autosomal dominant
Affected status: unknown
Allele origin:
unknown
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000883101.1
First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019 |
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Uncertain significance
(Oct 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Thrombophilia due to protein S deficiency, autosomal recessive
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000260947.6
First in ClinVar: Jan 31, 2016 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 501 of the PROS1 protein (p.Ser501Pro). … (more)
This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 501 of the PROS1 protein (p.Ser501Pro). This variant is present in population databases (rs121918472, gnomAD 0.3%), including at least one homozygous and/or hemizygous individual. This variant is known as the Heerlen variant, also reported as Ser460Pro. This variant has been reported in several individuals with type III protein S deficiency and it segregates with disease in multiple families but some carriers are unaffected (PMID: 7579448, 1547381, 12960605, 24119292). The pathogenicity of this variant is much debated in the literature with reports that argue for a pathogenic classification, a benign polymorphism as well as a modifier that works in synergy with other genetic factors. It has also been observed to segregate with disease in related individuals. This variant has been classified as a polymorphism in some reports because it is present at a similar frequency in controls as well as affected individuals (PMID: 2143091, 24014240) and it has been reported in unaffected family members (PMID: 15147381). In contrast, several studies report a statistically significant increase in the Heerlen allele frequency in individuals with low protein S levels and/or venous thrombosis (PMID: 8765219, 7579448, 10669162, 28374852). In addition, individuals homozygous for Heerlen have been reported to have lower protein S levels and a more severe type I form compared to individuals that are heterozygous (PMID: 10887114, 10669162). Finally, several reports suggest that the Heerlen variant shows synergy with other genetic risks for thrombosis such as Factor V Leiden and/or APC (activated protein C) variants (PMID: 8765219, 10669162, 20880255, 24365770). One functional study reports a synergy with Factor V Leiden mutation and a reduced capacity for the Heerlen variant to act as a co-factor for APC (PMID: 10887114). ClinVar contains an entry for this variant (Variation ID: 13316). 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 PROS1 protein function. In conclusion, there is evidence to support increased risk for protein S deficiency in heterozygous individuals and homozygous individuals show a more severe deficiency, although this variant has also been reported in unaffected family members and in control individuals. There is also evidence to support that the Heerlen variant alone has a mild effect but acts in synergy with other genetic factors. Because there is support for both a pro-pathogenic and a pro-benign effect, this sequence change has been classified as Uncertain Significance. (less)
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Uncertain significance
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary thrombophilia due to congenital protein S deficiency
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175577.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000303562.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Uncertain significance
(Feb 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966743.2
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Ser501Pro variant in PROS1 (also reported as p.Ser460Pro or PS Heerlen) has been identified in >20 individuals with protein S deficiency type III (Duchemin … (more)
The p.Ser501Pro variant in PROS1 (also reported as p.Ser460Pro or PS Heerlen) has been identified in >20 individuals with protein S deficiency type III (Duchemin 1995, Espinosa-Parrilla 2000, Beachamp 2004, ten Kate 2008, Varvenne 2011, Mulder 2012, Wypasek 2014). While the variant segregated with protein S deficiency in >10 affected family members (Duchemin 1995, Espinosa-Parrilla 2000, Beachamp 2004, ten Kate 2008), there were also multiple individuals in these families who had protein S deficiency but were negative for the p.Ser501Pro variant (Espinosa-Parrilla 2000, ten Kate 2008). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In vivo and in vitro functional studies provide some evidence that this variant may impact protein S function (Duchemin 1995, Denis 2005); however, these types of assays may not accurately represent biological function. This variant has also been identified in individuals with normal protein S levels (Espinosa-Parrilla 2000, Beauchamp 2004, ten Kate 2008) and in 0.33% (425/129150) of European chromosomes in gnomAD (http://gnomad.broadinstitute.org). The variant is also present in ClinVar with conflicting interpretations (Variation ID: 13316). While one meta-analysis has reported an odds ratio of 4-10 for venous thrombosis in French individuals who are heterozygous for this variant (Suchon 2017), this result has not been replicated. Furthermore, other studies find no association between this or other PROS1 variants and the risk for thrombosis (Alhenc-Gelas 2010, Pintao 2013). In summary, given the conflicting data regarding the impact of this variant on plasma protein S levels and risk for thrombosis, the clinical significance of the p.Ser501Pro variant is uncertain. ACMG/AMP criteria applied: PP1_Strong, PS3_Supporting, BS4, BS1_Supporting, BP4. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Feb 16, 2018)
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criteria provided, single submitter
Method: clinical testing
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Thrombophilia due to protein S deficiency, autosomal dominant
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001306866.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Oct 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001814825.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
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 … (more)
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) (less)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Thrombophilia due to protein S deficiency, autosomal dominant
Affected status: yes
Allele origin:
germline
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ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
Accession: SCV002500909.2
First in ClinVar: Apr 23, 2022 Last updated: Sep 10, 2022
Comment:
Submitted to GoldVariant by Kathleen Freson, Center for Molecular and Vascular Biology, Leuven, Belgium
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Observation 1:
Clinical Features:
Low protein S levels (present)
Observation 2:
Clinical Features:
Deep vein thrombosis (present) , Low protein S levels (present)
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Pathogenic
(Jul 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004227334.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5, PS3, PS4
Number of individuals with the variant: 7
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Pathogenic
(Jun 01, 2004)
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no assertion criteria provided
Method: literature only
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PROTEIN S HEERLEN
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000034492.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Bertina et al. (1990) reported an abnormal protein S that had a slightly lower molecular weight than normal, bound normally to C4BP (120830), and retained … (more)
Bertina et al. (1990) reported an abnormal protein S that had a slightly lower molecular weight than normal, bound normally to C4BP (120830), and retained full APC-cofactor activity. DNA analysis showed that the abnormality resulted from a T-to-C transition in the PROS1 gene, resulting in a ser460-to-pro (S460P) substitution within a potential glycosylation site. The variant was considered to be a neutral polymorphism and was estimated to be in 0.52% of healthy blood donors. Bertina et al. (1990) suggested that this variant, termed the 'Heerlen variant,' may be identical with the variant reported by Schwarz et al. (1989). Beauchamp et al. (2004) studied the molecular basis of free protein S deficiency in 7 individuals identified with persistently low plasma protein S levels from a survey of 3,788 Scottish blood donors. Five of the donors were found to be heterozygous for the Heerlen polymorphism. Haplotype analysis indicated a founder effect in 4 of the 5 donors. Beauchamp et al. (2004) estimated the prevalence of heritable protein S deficiency in the Scottish population to be between 0.16 and 0.21%, predominantly resulting from the presence of the Heerlen allele. Although all had persistently decreased free protein S, thrombotic events were not reported. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001554373.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The PROS1 p.Ser533Pro variant, also commonly referred to as the Heerlen variant, was identified in 141 of 11096 proband chromosomes (frequency: 0.0127) from individuals or … (more)
The PROS1 p.Ser533Pro variant, also commonly referred to as the Heerlen variant, was identified in 141 of 11096 proband chromosomes (frequency: 0.0127) from individuals or families with venous thrombosis or Protein S deficiency (Labrouche_2003_PMID:12960605, Bertina_1990_PMID:2143091, Suchon_2017_PMID:28374852, Borgel_1996_PMID:8765219).The variant was identified in dbSNP (ID: rs121918472) and ClinVar (classified as a VUS by Invitae and Equipe Genetique des Anomalies du Developpement, Université de Bourgogne in 2018 and as likely benign by PreventionGenetics). The variant was identified in control databases in 570 of 282838 chromosomes (1 homozygous) at a frequency of 0.002015 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 425 of 129150 chromosomes (freq: 0.003291), European (Finnish) in 37 of 25124 chromosomes (freq: 0.001473), Latino in 51 of 35432 chromosomes (freq: 0.001439), Other in 10 of 7226 chromosomes (freq: 0.001384), South Asian in 35 of 30616 chromosomes (freq: 0.001143), African in 9 of 24970 chromosomes (freq: 0.00036), Ashkenazi Jewish in 2 of 10368 chromosomes (freq: 0.000193), and East Asian in 1 of 19952 chromosomes (freq: 0.00005). Evidence for this variant’s role in protein S (encoded by PROS1) deficiency and venous thrombosis is conflicting. One study identified that the variant segregated with protein S deficiency in seven families, though a few carriers were unaffected (Duchemin_1995_PMID:7579448). Other studies have also found that the variant segregates with protein S deficiency, and that individuals homozygous for the Heerlen variant have been reported to have lower protein S levels and a more severe type I form compared to individuals that are heterozygous (Espinosa-Parilla_2000_PMID:10669162). Several studies report a statistically significant increase in the Heerlen allele frequency in individuals with low protein S levels and/or venous thrombosis (Borgel_1996_PMID:8765219, Duchemin_1995_PMID:7579448, Suchon_2017_PMID:28374852). However, other studies have identified the variant at a similar frequency in controls as well as affected individuals (PMID: Bertina_1990_2143091, Pintao_2013_PMID:24014240). One functional study reports a synergy with Factor V Leiden mutation and a reduced capacity for the Heerlen variant to act as a co-factor for APC (Giri_2010_PMID:10887114). Therefore it is unclear at this time if the Heerlen variant is pathogenic for venous thrombosis or Protein S deficiency, however it may contribute risk in conjuction with other genetic factors. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Ser533 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
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Uncertain significance
(Oct 09, 2023)
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no assertion criteria provided
Method: clinical testing
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Thrombophilia due to protein S deficiency, autosomal dominant
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004041785.1
First in ClinVar: Oct 14, 2023 Last updated: Oct 14, 2023 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Prevalence and in silico analysis of missense mutations in the PROS1 gene in the Swedish population: The SweGen dataset. | Zöller B | Thrombosis research | 2018 | PMID: 29883906 |
Genetic characterization of antithrombin, protein C, and protein S deficiencies in Polish patients. | Wypasek E | Polish archives of internal medicine | 2017 | PMID: 28607330 |
Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk. | Suchon P | Scientific reports | 2017 | PMID: 28374852 |
Impact of high risk thrombophilia status on recurrence among children and adults with VTE: An observational multicenter cohort study. | Brüwer G | Blood cells, molecules & diseases | 2016 | PMID: 27838551 |
Heerlen polymorphism associated with type III protein S deficiency and factor V Leiden mutation in a Polish patient with deep vein thrombosis. | Wypasek E | Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis | 2014 | PMID: 24365770 |
Protein S deficiency and Heerlen polymorphism in a Polish patient with acute myocardial infarction and previous venous thromboembolism. | Wypasek E | Thrombosis research | 2013 | PMID: 24119292 |
Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study. | Pintao MC | Blood | 2013 | PMID: 24014240 |
PROS1 Heerlen polymorphism is associated with increased free plasma tissue factor pathway inhibitor levels. | Mulder R | Thrombosis and haemostasis | 2012 | PMID: 22273984 |
Clinical consequences of compound heterozygosity for protein S mutation Heerlen and p.Cys252Gly protein S mutation. | Varvenne M | Thrombosis research | 2011 | PMID: 21764424 |
Protein S inherited qualitative deficiency: novel mutations and phenotypic influence. | Alhenc-Gelas M | Journal of thrombosis and haemostasis : JTH | 2010 | PMID: 20880255 |
Confirmation of inherited protein S deficiency by PROS1 mutational screening: Identification of three novel PROS1 mutations and haplotype analysis of p.Q279X recurrence. | Hurtado B | Thrombosis and haemostasis | 2008 | PMID: 18841302 |
PROS1 analysis in 87 pedigrees with hereditary protein S deficiency demonstrates striking genotype-phenotype associations. | Ten Kate MK | Human mutation | 2008 | PMID: 18435454 |
In vivo clearance of human protein S in a mouse model: influence of C4b-binding protein and the Heerlen polymorphism. | Denis CV | Arteriosclerosis, thrombosis, and vascular biology | 2005 | PMID: 16100035 |
The Ser460Pro mutation in recombinant protein S Heerlen does not affect its APC-cofactor and APC-independent anticoagulant activities. | Koenen RR | Thrombosis and haemostasis | 2004 | PMID: 15175796 |
The prevalence of, and molecular defects underlying, inherited protein S deficiency in the general population. | Beauchamp NJ | British journal of haematology | 2004 | PMID: 15147381 |
Protein C and protein S assessment in hospital laboratories: which strategy and what role for DNA sequencing? | Labrouche S | Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis | 2003 | PMID: 12960605 |
Deficient APC-cofactor activity of protein S Heerlen in degradation of factor Va Leiden: a possible mechanism of synergism between thrombophilic risk factors. | Giri TK | Blood | 2000 | PMID: 10887114 |
Homozygosity for the protein S Heerlen allele is associated with type I PS deficiency in a thrombophilic pedigree with multiple risk factors. | Espinosa-Parrilla Y | Thrombosis and haemostasis | 2000 | PMID: 10669162 |
Molecular basis for protein S hereditary deficiency: genetic defects observed in 118 patients with type I and type IIa deficiencies. The French Network on Molecular Abnormalities Responsible for Protein C and Protein S Deficiencies. | Borgel D | The Journal of laboratory and clinical medicine | 1996 | PMID: 8765219 |
The Ser 460 to Pro substitution of the protein S alpha (PROS1) gene is a frequent mutation associated with free protein S (type IIa) deficiency. | Duchemin J | Blood | 1995 | PMID: 7579448 |
Diagnosis and surgical treatment of five cases of triple shunt (ASD + VSD + PDA). | Kubota M | Surgery today | 1992 | PMID: 1547381 |
Heerlen polymorphism of protein S, an immunologic polymorphism due to dimorphism of residue 460. | Bertina RM | Blood | 1990 | PMID: 2143091 |
Familial protein S deficiency with a variant protein S molecule in plasma and platelets. | Schwarz HP | Blood | 1989 | PMID: 2526663 |
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Text-mined citations for rs121918472 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.