NM_000173.7(GP1BA):c.746G>T (p.Gly249Val) AND Pseudo von Willebrand disease

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 20, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000004370.7

Allele description [Variation Report for NM_000173.7(GP1BA):c.746G>T (p.Gly249Val)]

NM_000173.7(GP1BA):c.746G>T (p.Gly249Val)

Gene:

GP1BA:glycoprotein Ib platelet subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_000173.7(GP1BA):c.746G>T (p.Gly249Val)

Other names:

G233V

HGVS:

NC_000017.11:g.4933350G>T
NG_008767.2:g.6056G>T
NM_000173.7:c.746G>TMANE SELECT
NP_000164.5:p.Gly249Val
LRG_480t1:c.746G>T
LRG_480:g.6056G>T
LRG_480p1:p.Gly249Val
NC_000017.10:g.4836645G>T
NM_000173.6:c.746G>T
P07359:p.Gly249Val

Protein change:

G249V; GLY233VAL

Links:

UniProtKB: P07359#VAR_005261; OMIM: 606672.0003; dbSNP: rs121908062

NCBI 1000 Genomes Browser:

rs121908062

Molecular consequence:

NM_000173.7:c.746G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Pseudo von Willebrand disease (VWDP)
Synonyms:: BLEEDING DISORDER, PLATELET-TYPE, 3; Platelet-type von Willebrand disease
Identifiers:: MONDO: MONDO:0008332; MedGen: C1280798; Orphanet: 52530; OMIM: 177820

Recent activity

Clear Turn Off Turn On

Gene Links for GEO Profiles (Select 118344674) (1)
Gene
TXNRD2 thioredoxin reductase 2 [Homo sapiens]
TXNRD2 thioredoxin reductase 2 [Homo sapiens]
Gene ID:10587

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000024541	OMIM	no assertion criteria provided	Pathogenic (May 1, 1993)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 2052556, 8486780
SCV002500877	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	paternal, maternal, unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34355501, 25741868
SCV002556895	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 20, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000024541

OMIM

no assertion criteria provided

Pathogenic
(May 1, 1993)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV002500877

ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

paternal, maternal, unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002556895

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 20, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	paternal	yes	3	not provided	not provided	3	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	maternal	yes	6	not provided	not provided	6	not provided	clinical testing
not provided	unknown	yes	22	not provided	not provided	22	not provided	clinical testing

Citations

PubMed

Mutation in the gene encoding the alpha chain of platelet glycoprotein Ib in platelet-type von Willebrand disease.

Miller JL, Cunningham D, Lyle VA, Finch CN.

Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4761-5.

PubMed [citation]

PMID:: 2052556
PMCID:: PMC51746

Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment.

Murata M, Russell SR, Ruggeri ZM, Ware J.

J Clin Invest. 1993 May;91(5):2133-7.

PubMed [citation]

PMID:: 8486780
PMCID:: PMC288214

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000024541.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Platelet-type von Willebrand disease (177820), also known as pseudo-von Willebrand disease, is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by patients' platelets. In 7 affected members of a family with pseudo-VWD, Miller et al. (1991) identified a heterozygous mutation in the GP1BA gene resulting in the substitution of gly233-to-val (G233V). The mutation was absent in 6 unaffected family members. To evaluate the functional consequences of the G233V mutation, Murata et al. (1993) constructed a recombinant analog of the alpha subunit of GP Ib containing val233. The recombinant fragment with the val233 substitution reproduced the functional abnormality of the GP Ib-IX complex in platelet-type von Willebrand disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV002500877.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)
2	not provided	1	not provided	not provided	clinical testing	PubMed (2)
3	not provided	1	not provided	not provided	clinical testing	PubMed (2)
4	not provided	1	not provided	not provided	clinical testing	PubMed (2)
5	not provided	1	not provided	not provided	clinical testing	PubMed (2)
6	not provided	1	not provided	not provided	clinical testing	PubMed (2)
7	not provided	1	not provided	not provided	clinical testing	PubMed (2)
8	not provided	1	not provided	not provided	clinical testing	PubMed (2)
9	not provided	1	not provided	not provided	clinical testing	PubMed (2)
10	not provided	1	not provided	not provided	clinical testing	PubMed (2)
11	not provided	1	not provided	not provided	clinical testing	PubMed (2)
12	not provided	1	not provided	not provided	clinical testing	PubMed (2)
13	not provided	1	not provided	not provided	clinical testing	PubMed (2)
14	not provided	1	not provided	not provided	clinical testing	PubMed (2)
15	not provided	1	not provided	not provided	clinical testing	PubMed (2)
16	not provided	1	not provided	not provided	clinical testing	PubMed (2)
17	not provided	1	not provided	not provided	clinical testing	PubMed (2)
18	not provided	1	not provided	not provided	clinical testing	PubMed (2)
19	not provided	1	not provided	not provided	clinical testing	PubMed (2)
20	not provided	1	not provided	not provided	clinical testing	PubMed (2)
21	not provided	1	not provided	not provided	clinical testing	PubMed (2)
22	not provided	1	not provided	not provided	clinical testing	PubMed (2)
23	not provided	1	not provided	not provided	clinical testing	PubMed (2)
24	not provided	1	not provided	not provided	clinical testing	PubMed (2)
25	not provided	1	not provided	not provided	clinical testing	PubMed (2)
26	not provided	1	not provided	not provided	clinical testing	PubMed (2)
27	not provided	1	not provided	not provided	clinical testing	PubMed (2)
28	not provided	1	not provided	not provided	clinical testing	PubMed (2)
29	not provided	1	not provided	not provided	clinical testing	PubMed (2)
30	not provided	1	not provided	not provided	clinical testing	PubMed (2)
31	not provided	1	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	paternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
4	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
5	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
6	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
7	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
8	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
9	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
10	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
11	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
12	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
13	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
14	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
15	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
16	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
17	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
18	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
19	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
20	paternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
21	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
22	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
23	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
24	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
25	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided
26	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
27	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
28	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
29	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
30	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
31	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Genetics and Molecular Pathology, SA Pathology, SCV002556895.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The GP1BA c.746G>T variant is classified as Likely Pathogenic (PS3, PM2, PP1, PP3, PP4, PP5)

#	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

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine