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NM_000552.5(VWF):c.4196G>A (p.Arg1399His) AND VWF-related condition

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 30, 2023
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:
RCV003415597.5

Allele description

NM_000552.5(VWF):c.4196G>A (p.Arg1399His)

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.4196G>A (p.Arg1399His)
HGVS:
  • NC_000012.12:g.6019222C>T
  • NG_009072.2:g.110449G>A
  • NM_000552.5:c.4196G>AMANE SELECT
  • NP_000543.3:p.Arg1399His
  • LRG_587t1:c.4196G>A
  • LRG_587:g.110449G>A
  • LRG_587p1:p.Arg1399His
  • NC_000012.11:g.6128388C>T
  • NG_009072.1:g.110449G>A
  • NM_000552.3:c.4196G>A
  • NM_000552.4:c.4196G>A
  • P04275:p.Arg1399His
Protein change:
R1399H; ARG1399HIS
Links:
UniProtKB: P04275#VAR_005805; OMIM: 613160.0010; dbSNP: rs1800382
NCBI 1000 Genomes Browser:
rs1800382
Molecular consequence:
  • NM_000552.5:c.4196G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
VWF-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004117563PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 30, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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 PreventionGenetics, part of Exact Sciences, SCV004117563.2

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

Description

The VWF c.4196G>A variant is predicted to result in the amino acid substitution p.Arg1399His. This variant was reported in healthy controls and in VWD type 1 and type 2 patients, some of whom had other likely pathogenic VWF gene variants (Borràs et al. 2017. PubMed ID: 28971901; Flood et al. 2015. PubMed ID: 25662333; Perez-Rodriquez et al. 2018. PubMed ID: 29924855). Amino acid residue p.Arg1399 resides in the VWF A1 collagen binding domain. Data in Flood et al. and in another report, Slobodianuk et al. 2018. PubMed ID: 30565388, indicate that the p.Arg1399His substitution decreases type IV and VI collagen binding. A similar variant, c.4195C>T (p.Arg1399Cys) was also reported in a patient with VWF 2m (Gadisseur et al. 2009. PubMed ID: 19506359). However, the p.Arg1399His substitution occurs frequently in several populations, including in the homozygous state, and is reported at frequencies ranging from ~ 0.2 -1.6%. Although we suspect that the c.4196G>A (p.Arg1399His) variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic information.

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

Last Updated: May 12, 2024