U.S. flag

An official website of the United States government

NM_000552.5(VWF):c.4135C>T (p.Arg1379Cys) AND VWF-related disorder

Germline classification:
Pathogenic (1 submission)
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003335097.1

Allele description [Variation Report for NM_000552.5(VWF):c.4135C>T (p.Arg1379Cys)]

NM_000552.5(VWF):c.4135C>T (p.Arg1379Cys)

Gene:
VWF:von Willebrand factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p13.31
Genomic location:
Preferred name:
NM_000552.5(VWF):c.4135C>T (p.Arg1379Cys)
Other names:
p.R1379C
HGVS:
  • NC_000012.12:g.6019283G>A
  • NG_009072.2:g.110388C>T
  • NM_000552.5:c.4135C>TMANE SELECT
  • NP_000543.3:p.Arg1379Cys
  • LRG_587t1:c.4135C>T
  • LRG_587:g.110388C>T
  • LRG_587p1:p.Arg1379Cys
  • NC_000012.11:g.6128449G>A
  • NG_009072.1:g.110388C>T
  • NM_000552.2:c.4135C>T
  • NM_000552.3:c.4135C>T
  • NM_000552.4:c.4135C>T
Protein change:
R1379C
Links:
dbSNP: rs61750074
NCBI 1000 Genomes Browser:
rs61750074
Molecular consequence:
  • NM_000552.5:c.4135C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
VWF-related disorder
Synonyms:
VWF-related disorders; VWF-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004046395Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046395.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant has been previously reported as a heterozygous and compound heterozygous change in patients with VWF-related disorders (PMID: 11325649, 27785872, 16985174, 19277422, 26986123, 31939074). Functional studies show the p.Arg1379Cys variant enhances binding capacity to the glycoprotein Ib-alpha (PMID: 27785872). This variant was shown to segregate with disease in an autosomal dominant manner in at least one family with VWF-related disorder and a phenotype of mild bleeding (PMID: 20305138). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (6/281706) and thus is presumed to be rare. In silico tools used to predict the effect of this variant on protein function yield discordant results. Based on the available evidence, the c.4135C>T (p.Arg1379Cys) variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024