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NM_000552.4(VWF):c.3922C>T (p.Arg1308Cys)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Dec 31, 2020)
Last evaluated:
Dec 16, 2019
Accession:
VCV000000289.5
Variation ID:
289
Description:
single nucleotide variant
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NM_000552.4(VWF):c.3922C>T (p.Arg1308Cys)

Allele ID
15328
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12p13.31
Genomic location
12: 6019496 (GRCh38) GRCh38 UCSC
12: 6128662 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.6128662G>A
NC_000012.12:g.6019496G>A
NM_000552.4:c.3922C>T NP_000543.2:p.Arg1308Cys missense
... more HGVS
Protein change
R1308C
Other names
-
Canonical SPDI
NC_000012.12:6019495:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
OMIM: 613160.0006
dbSNP: rs61749387
ClinGen: CA114125
UniProtKB: P04275#VAR_005795
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, single submitter Jul 9, 2019 RCV000000313.3
Likely pathogenic 2 criteria provided, single submitter Oct 2, 2019 RCV000086703.2
Pathogenic 1 criteria provided, single submitter Feb 1, 2019 RCV000851770.1
Pathogenic 1 criteria provided, single submitter Dec 16, 2019 RCV001284955.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
VWF - - GRCh38
GRCh37
1003 1057

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Feb 01, 2019)
criteria provided, single submitter
Method: research
von Willebrand disorder
Allele origin: unknown
NIHR Bioresource Rare Diseases, University of Cambridge
Study: ThromboGenomics
Accession: SCV000899705.1
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (1)
Pathogenic
(Jul 09, 2019)
criteria provided, single submitter
Method: clinical testing
von Willebrand disease, type 2b
Allele origin: germline
Versiti Diagnostic Laboratories,Versiti, Inc
Accession: SCV001250574.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (6)
Comment:
The missense variant VWF c.3922C>T, p.Arg1308Cys (p.R1308C; legacy p.R545C) in exon 28 changes amino acid arginine at codon 1308 to cysteine. The arginine at this … (more)
Likely pathogenic
(Oct 02, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000889912.2
Submitted: (Dec 31, 2020)
Evidence details
Publications
PubMed (13)
Comment:
Not found in the total gnomAD dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. … (more)
Pathogenic
(Dec 16, 2019)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV001471056.1
Submitted: (Dec 11, 2020)
Evidence details
Comment:
The VWF c.3922C>T; p.Arg1308Cys variant (rs61749387), also known as R545C, is reported in the literature in multiple individuals affected with von Willebrand disease type 2B … (more)
Pathogenic
(May 01, 2010)
no assertion criteria provided
Method: literature only
VON WILLEBRAND DISEASE, TYPE 2B
Allele origin: germline
OMIM
Accession: SCV000020457.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (5)
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
Academic Unit of Haematology, University of Sheffield
Accession: SCV000118907.1
Submitted: (Jul 31, 2012)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders. Downes K Blood 2019 PMID: 31064749
Genetic variants of VWF gene in type 2 von Willebrand disease. Freitas SDS Haemophilia : the official journal of the World Federation of Hemophilia 2019 PMID: 30817071
Higher and lower active circulating VWF levels: different facets of von Willebrand disease. Casonato A British journal of haematology 2015 PMID: 26456374
The co-influence of VWD type 2B/2M mutations in the A1 domain and platelet GPIbα on the rate of cleavage to VWF by ADAMTS13. Ma Z Thrombosis research 2015 PMID: 26345337
First report of inhibitory von Willebrand factor alloantibodies in type 2B von Willebrand disease. Baaij M British journal of haematology 2015 PMID: 25851809
Management of pregnancy in type 2B von Willebrand disease: case report and literature review. Biguzzi E Haemophilia : the official journal of the World Federation of Hemophilia 2015 PMID: 25431025
von Willebrand factor, Jedi knight of the bloodstream. Springer TA Blood 2014 PMID: 24928861
Characterisation of mutations and molecular studies of type 2 von Willebrand disease. Ahmad F Thrombosis and haemostasis 2013 PMID: 23179108
Pregnancy in type 2B VWD: a case series. Ranger A Haemophilia : the official journal of the World Federation of Hemophilia 2012 PMID: 22077376
The genetic basis of von Willebrand disease. Goodeve AC Blood reviews 2010 PMID: 20409624
Biochemical characterization of a recombinant von Willebrand factor (VWF) with combined type 2B and type 1 defects in the VWF gene in two patients with a type 2A phenotype of von Willebrand disease. Baronciani L Journal of thrombosis and haemostasis : JTH 2007 PMID: 17155947
Expression studies on a novel type 2B variant of the von Willebrand factor gene (R1308L) characterized by defective collagen binding. Baronciani L Journal of thrombosis and haemostasis : JTH 2005 PMID: 16246252
Search for mutations in a segment of the exon 28 of the human von Willebrand factor gene: new mutations, R1315C and R1341W, associated with type 2M and 2B variants. Casaña P American journal of hematology 1998 PMID: 9723578
A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease. Hagiwara T Thrombosis and haemostasis 1996 PMID: 8865541
Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden. Donnér M British journal of haematology 1992 PMID: 1419803
Molecular basis of von Willebrand disease type IIB. Candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences. Randi AM The Journal of clinical investigation 1991 PMID: 2010538
An Arg545----Cys545 substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease. Donnér M European journal of haematology 1991 PMID: 1761120

Text-mined citations for rs61749387...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jan 30, 2021