PMID: 20940419

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: No proband or variant information; however, there is potential experimental assay information

PMID: 18180086

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article gives background information on GT; there is no mention of GT probands with variants in ITGA2B and/or ITGB3

Supplementary Table S1 & S2 Proband and Variant Information:

Case20: GT23, Male, 19, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000225, HP:0000421

(Easy bruising, gingival bleeding, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.1031A>C (p.Tyr344Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025814

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case6: GT7, Female, 19, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 brother, that is all the information Supp table S1 gives us

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 and HP:0000421

(Easy bruising and epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <10-15% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent ADP but some response with other agonists (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.187C>T (p.Arg63Cys) and NM_000212.2:c.505C>T (p.Arg169Ter)

LegacyVariant: N/A

ClinVar: 631774

CAiD: CA8622892 and CA291224658

gnomAD: MAF in the East Asian population is 0.00005012 http://gnomad.broadinstitute.org/variant/17-45360741-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case54: GT54, Male, 33, Argintinian/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0006298

(Gingival bleeding, bleeding following tooth extraction)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.2014+1G>A and a "LR deletion variant" as mentioned in Sup Table 1

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400033055

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case11: GT12, Female, 61, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Brother (died at birth) this is all the information Supp table S1 gives

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978, HP:0000790

(Epistaxis, easy bruising, hematuria)

CaseHPOFreeText: Heavy bleeding and menarche

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% variant expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.565C>T (p.Pro189Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

gnomAD: MAF in the European (non-Finnish) population 0.00002638 http://gnomad.broadinstitute.org/variant/17-45362012-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case59: GT61, Female, 49 years old, French/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000132

(Easy bruising, menorrhagia)

CaseHPOFreeText: Tonsil bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.224del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: MAF in the European (non-Finnish) population is 0.000008795 https://gnomad.broadinstitute.org/variant/17-45360777-TG-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case32: GT35b, Female, 16 years old, USA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is 35a in this study (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B and ITGB3

Variant: ITGB3: NM_000212.2:c.392G>C (p.Arg131Pro) and NM_000212.2:c.777+1G>A ITGA2B: NM_000419.3:c.2264G>A (p.Arg755Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

gnomAD: MAF in the African population is 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C, MAF in the Latino population is 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A, MAF in the Latino population is 0.0001903 http://gnomad.broadinstitute.org/variant/17-42454380-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case5: GT6, Female, 19, French/Algerian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 and HP:0000225

(Easy bruising, gingival bleeding)

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asl314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case29: GT33b, Female, age not specified, USA/Laos

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 33a in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: Life-threatening bleeding at onset of menses

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8623443

gnomAD: MAF in the Other population is 0.0001385 http://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case18: GT21, Female, 61, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.2864T>A (p.Leu955Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA399791171

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case67: GT70, Female, 21 years old, French/Arab

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0002239, HP:0000421, HP:0000132

(Bruising, purpura, GI bleeding, epistaxis, menorrhagia)

CaseHPOFreeText: Hematomas, oropharynx bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.613_614+2del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940309

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case43: GT43a, Female, 7 years old, Moroccan (this proband died from epistaxis-see Supp Table S1)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother is 43b (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Severe epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.614+1G>T and NM_000212.2:c.683G>A (p.Arg228His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023344 and CA8623025

gnomAD: MAF in the African population is 0.00008012 http://gnomad.broadinstitute.org/variant/17-45363694-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case50: GT50, Male, 78 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000225

(Ecchymosis, gingival bleeding)

CaseHPOFreeText: Moderate bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.1260G>A (p.Lys376_Thr420del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623200

gnomAD: MAF in the African population is 0.00004005 http://gnomad.broadinstitute.org/variant/17-45368454-G-A

PMID: 10418797

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient; however, there is no mention of variants in ITGA2B and/or ITGB3; therefore, there is insufficient evidence

PreviouslyPublished: The GT patient in this article has been previously published in this PMID: 2180491

Supplementary Table S1:

Case41: GT48, French, gender and age not specified here at this time

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets

PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists

CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene

Gene: ITGB3

Variant: NM_000212.2:c.1094A>G (p.Asn365Ser) and NM_000212.2:c.1522del (p.Gln508SerfsTer161)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400026292 and CA772541579

gnomAD: N/A

Supplementary Table S1:

Case47: GT54, Arg/Italian, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets

PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists

CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene

Gene: ITGB3

Variant: NM_000212.2:c.2014+5G>A and the other variant is a "LR deletion" which is all thats mentioned

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940701

gnomAD: N/A

Supplementary Table S1:

Case5: GT 6, French/Algerian, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets

PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists

CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asp314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

gnomAD: N/A

Supplementary Table S1:

Case62: GT73, French, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets

PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists

CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene

Gene: ITGB3

Variant: NM_000212.2:c.889G>A (p.Gly297Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623074

gnomAD: MAF in the European (non-Finnish) population is 0.00002643 https://gnomad.broadinstitute.org/variant/17-45364547-G-A

Supplementary Table S1:

Case44: GT51, French/African, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets

PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists

CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene

Gene: ITGB3

Variant: NM_000212.2:c.861del (p.Arg287SerfsTer34) and NM_000212.2:c.1456del (p.Cys486A;afsTer183)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940375 and CA915940376

gnomAD: N/A

Case1: Patient F1P1, Male, 11 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000978

(Gingival bleeding, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGB3

Variant: NM_000212.2:c.176T>C (p.Leu59Pro) and NM_000212.2:c.1143A>C (p.Val381Val) and NM_000212.2:c.1545G>A (p.Arg515Arg) and the other variant stated here is g.41037G>C which I am marking as an Unknown Variant-- biocurator should look at this and determine variant

LegacyVariant: N/A

ClinVar: 13558 (p.Leu59Pro), 255535 (p.Val381Val), 255537 (p.Arg515Arg)

CAiD: CA123235 (p.Leu59Pro), CA8623175 (p.Val381Val), CA8623284 (p.Arg515Arg)

gnomAD: MAF in the Ashkenazi Jewish population is 0.1565 https://gnomad.broadinstitute.org/variant/17-45360730-T-C for (p.Leu59Pro) and MAF in the East Asian population is 0.5857 https://gnomad.broadinstitute.org/variant/17-45368337-A-C for (p.Val381Val) and MAF in the East Asian population for (p.Arg515Arg) is 0.3455 https://gnomad.broadinstitute.org/variant/17-45369789-G-A

PMID: 30325339

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

PMID: 12411291

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention GT probands with variants in ITGA2B and/or ITGB3 therefore there is no evdience; however, there may be potenetial experimental assay information

PMID: 1826081

Gene: ITGA2B and ITGB3 (we are noting these gene names even though there is no evidence for GT in this article, because we are curating for these genes-- CThaxton advised it would be a good idea to always note down Genes and HGNC)

HGNC: 6138 and 6156

NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report. The studies performed in this article were undertaken to characterize the interaction of platelets with laminin.

Case6: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0031364

(Epistaxis, gingival bleeding, menorrhagia, ecchymosis)

CaseHPOFreeText: Post-partum bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case13: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364, HP:0000132, HP:0002239, HP:0002573

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia, gastrointestinal bleeding, rectal bleeding)

CaseHPOFreeText: Haemarthrosis, DIC

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case20: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364, HP:0000132

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia)

CaseHPOFreeText: Larynx bleeding, haematuria

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case5: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0002573

(Gingival bleeding, rectal bleeding)

CaseHPOFreeText: Post-partum bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case7: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364, HP:0030137

(Epistaxis, gingival bleeding, ecchymosis, prolonged bleeding following circumcision)

CaseHPOFreeText: Haematuria

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case3: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0030137, HP:0000421, HP:0000225, HP:0031364, HP:0002249

(Prolonged bleeding following circumcision, epistaxis, ecchymosis, melena)

CaseHPOFreeText: Haematemesis

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: HGVS nomenclature not available. p.Val721Cysfs*33

LegacyVariant: p.Val695Cysfs*33

ClinVar: 13563

CAiD: N/A

gnomAD: N/A

2:20-3:30

Case19: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364

(Epistaxis, gingival bleeding, ecchymosis)

CaseHPOFreeText: Intra-cerebral post-trauma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case4: No gender, age, or ethnicity provided. Patient followed in Germany

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.

Gene: ITGB3

Variant: NM_000212.2:c.1717T>C (p.Cys573Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032387

gnomAD: N/A

Case9: Female, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.

Gene: ITGB3 and ITGA2B

Variants: NM_000212.2:c.353T>A (p.Leu118His), NM_000212.2:c.1732G>A (p.Asp578Asn)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224511 (p.Leu118His- ITGB3), CA8623343 (p.Asp578Asn- ITGB3)

gnomAD: MAF for p.Asp578Asn variant in "Other" population: 0.0008149 https://gnomad.broadinstitute.org/variant/17-45376715-G-A

Case7: Female, elderly (age not specified)

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding when younger

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.

Gene: ITGB3

Variant: NM_000212.2:c.565C>T (p.Pro189Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

gnomAD: MAF in the European (non-Finnish) population is 0.00002638 https://gnomad.broadinstitute.org/variant/17-45362012-C-T

PMID: 22928124

Genes: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article reports a case of acute catastrophic vaginal bleeding in a girl, who was diagnosed with GT and responded to uterine tamponade for acute control of vaginal bleeding; however, no variants in ITGA2B and/or ITGB3 are mentioned in this article therefore we have insufficient evidence

PMID: 9021812

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report

PMID: 1788826

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence

PMID: 9845537

Gene: ITGB3

HGNC: 6156

Case1: Female, 20 years old, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See pedigree in Fig 2

ParentalGenotype: Parental genotype given see Fig 2

CasePresentingHPOs: HP:0000978 (Easy bruising)

CaseHPOFreeText: Mucocutaneous bleeding, menstrual hemorrhages

CaseNotHPOs: N/A

ProteinExpression: The absence of platelet GPIIb-IIIa complexes by flow cytometric analysis with MoAbs was performed and shown

Platelet Aggregation: No response detected either spontaneously or in response to agonists (this is all of the information we are given)

CasePreviousTesting: GPIIb and GPIIIa genes were screened for mutations by SSCP of PCR amplified exons from genomic DNA

Gene: ITGB3

Variant: NM_000212.2:c.1924G>T (p.Glu642Ter)

LegacyVariant: (p.Glu616Ter)

ClinVar: 13565

CAiD: CA123249

gnomAD N/A

PMID: 10712380

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This review mentions many variants in ITGA2B and ITGB3; however, there are no probands to tie these variants to therefore there is insufficient evidence

Case1: Female, 35 years old, Italian

DiseaseAssertion: Macrothromocytopenia

FamilyInfo: See Supp. Fig S1 for pedigree

ParentalGenotype: See Supp. Fig S1 for pedigree

CasePresentingHPOs: N/A

CaseHPOFreeText: Life-long moderate to severe bleeding, mainly mucocutaneous

CaseNotHPOs: N/A

CaseNotHPOsFreeText: No abnormalities in blood clotting

ProteinExpression: Flow cytometry showed mild reduction of surface αIb β3

PlateletAggregation: Impaired platelet aggregation to physiological agonists but not to ristocetin,

CasePreviousTesting: ITGA2B and ITGB3 were amplified and sequenced

Gene: ITBG3

Variant: NM_000212.2:c.2134+1G>C

LegacyVariant: N/A

ClinVar: 50228

CAiD: CA143711

gnomAD: N/A

PMID: 19336737

Gene: ITGB3

HGNC: 6156

Case#: Kuijers_1993_NAIT boy_male_>1 y.o.

DiseaseAssertion:

FamilyInfo: All members of this large family were healthy and none had a history of a bleeding tendency or a tendency for thrombosis and/or embolism. There was no previous case of NAIT in the family. Routine blood counts were normal. From the segregation pattern in the family, it can be concluded that the Mo antigen is inherited as an autosomal dominant allele

ParentalGenotype: One affect (likely homozygous) and one unaffected (not carrying)

CasePresentingHPOs: HP:0000967 Petechiae, HP:0007420 Spontaneous hematomas,

PlateletAggregation:

CaseHPOFreeText: hemoglobin (Hb) count of 13.1 mmol/L, hematocrit (Ht) 0.61, leukocyte count 36.6 × 106/L (3 hours postpartum), Gastrointestinal tract bleedings (2 days postpartum). s treated with high-dose intravenous Ig (IVIg) (0.4 g/kg) for 3 days. The platelet count stabilized and started to increase slowly to 46 × 109 in the following weeks

CaseNotHPOs:

CaseNotHPOFreeText:

ProteinExpression: Western blotting showed that the antigen resides on platelet glycoprotein IIIa

CasePreviousTesting:

Method: PCR coding region

PreviouslyPublished:

Gene: ITGB3

Variant: NM_000212.3:c. _C>G (C → G at base 1267 was observed. This C → G mutation changes a CCC codon for proline into a GCC that codes for alanine at amino acid 407 of the mature GP IIIa DNA.) (No other base-pair changes in the entire GP IIIa cDNA were noticed.)

HGVS:

ClinVar:

CAID:

gnomAD:

Affected: 11

Unaffected: 20

Segregations: 11

eLOD: 3.31

PMID: 2565345

Gene: ITGB3

HGNC: 6153

PMID: 18840725

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article is a review discussing the integrin αIIbβ3, there is no mention of probands with variants in ITGA2B and/or ITGB3

Case31: Patient ET

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000132

(Bruising, epistaxis, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.719G>A (p.Arg240Gln)

LegacyVariant: N/A

ClinVar: 13553

CAiD: CA123224

gnomAD: N/A

PreviouslyPublished: Reference 52

Case25: "Cam"

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: >20,000/platelet +/- Ca2+

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.433G>T (p.Asp145Tyr)

LegacyVariant: N/A

ClinVar: 13554

CAiD: CA123226

gnomAD: N/A

PreviouslyPublished: References 41,42

Case34: Patient LD

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 30% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.847del and NM_000212.2:c.863T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940765 and CA400024958

gnomAD: N/A

PreviouslyPublished: Reference 56

PMID: 9215749

Gene: ITGA2B and ITGB3

HGNC: 6138 abd 6156

Case24: Pakistan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.428T>G (p.Leu143Trp)

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45361875-T-G

PreviouslyPublished: Reference number 28

Case26: Patient NR

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000978

(Epistaxis, gingival bleeding, bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.433G>T (p.Asp145Tyr)

LegacyVariant: N/A

ClinVar: 13554

CAiD: CA123226

gnomAD: N/A

PreviouslyPublished: Ref 43

Case27: Patient BL

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000225

(Bruising, epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 30% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.563C>T (p.Ser188Leu)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622981

gnomAD: MAF in the European non Finnish population is 0.000008793 https://gnomad.broadinstitute.org/variant/17-45362010-C-T

PreviouslyPublished: Reference 44

Case35: Patient Chinese 20 (found in GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000132, HP:0000979, HP:0000967

(Epistaxis, menorrhagia, purpura/petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <15% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.1199G>A (Cys400Tyr)

LegacyVariant: N/A

ClinVar: 13562

CAiD: CA123244

gnomAD: N/A

PreviouslyPublished: References 57 and 58

Case40: Patient P

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 44% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NC_000017.11:g.47310169T>C

LegacyVariant: N/A

ClinVar: 13556

CAiD: CA123230

gnomAD: N/A

PreviouslyPublished: References 63-65

PMID: 9351872

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article is a review on GT

PMID: 18450741

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InusufficientEvidence: This article used a bifunctional bioengineered disintegrin/alkaline phosphatase hybrid protein ErAPv to evaluate 14 consecutive cases of Glanzmann thrombasthenia and 20 normal healthy controls. Thererefore, GT probands are mentioned; however, no specific variants in ITGA2B and/or ITBG3 have been mentioned in these patients

PMID: 29063905

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a case of an individual with Glanzmann thrombasthenia; however, no specific variants mentioned in proband.

Case11: Patient Ssyl

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGB3

Variant: NM_000212.2:c.1955A>T (p.His652Leu)

LegacyVariant: (p.His626Leu)

ClinVar: N/A

CAiD: CA400032927

gnomAD: N/A

PMID: 11798398

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

PMID: 11823541

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions 1 GT proband; however, variants in ITGA2B and/or ITGB3 are not mentioned.

PMID: 2014236

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article does not mention specific case reports- rather, this article mentions two different populations harboring variants. I have annotated the 2 variants each cohort harbors

PMID: 28395882

Gene: ITGA2B and ITGB3

HGNC: 6139 and 6156

PMID: 30216638

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions mothers with GT and their newborns. Table 1 shows very general/vague genetic data for the mothers, it is not easy to determine what the actual genetic defects are from Table 1; therefore, there is insufficient evidence

Supplementary Tables 1 and 2 combined information:

Case42: GT42, Female, 9 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGB3

Variant: NM_000212.2:c.1300del (p.Gln434fs) Note in google doc to ask

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940256

gnomAD: N/A

PMID: 29675921

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156, respectively as gene names shown above

Supplementary Tables 1 and 2 combined information:

Case15b: Male, 9 years old, brother to GT15a

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1, brother to GT15a

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225

(Bruising, purpura, ecchymosis, epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed a small response to ADP and collagen but normal response to ristocetin

CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.

Gene: ITGB3

Variant: NM_000212.2:c.1525del (p.Gln509Argfs*160) and NM_000212.2:c.1199G>A (p.Cys400Tyr)

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

CAiD: CA915940237 (p.Gln509Argfs*160) and CA123244 (p.Cys400Tyr)

gnomAD: N/A

Case1: Male, 67, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 Bruising susceptibility (From previously published PMID: 9226191)

CaseHPOFreeText: Moderate bleeding tendency

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Platelets failed to aggregate and bind to fibrinogen in response to ADP, collagen, and thrombin but were able to support a subnormal clot retraction and the amount of αIIbβ3 complexes was estimated to be about 50% of the normal value (From previously published PMID: 9226191)

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2332T>C (p.Ser778Pro) (See Table 1)

LegacyVariant: p.Ser752Pro

ClinVar: 13556

CAiD: CA123230

gnomAD: N/A

PreviouslyPublished: PMID: 9226191

PMID: 27221710

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention GT probands with variants in ITGA2B or ITGB3

PMID: 21567370

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a proband with GT; however, no mention of the proband with variants in ITGA2B and ITGB3

Case15: Patient ID O, Female, 7 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406, HP:0000225

(Recurrent epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000967, HP:0000979, HP:0000978, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, easy bruising, GI bleeding, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dental, hemorrhage after trauma, ear bleeding, hematoma

ProteinExpression: N/A

PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin

CasePreviousTesting: Exon PCR was used to amplify coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available

Gene: ITGB3

Variant: NM_000212.2:c.2080C>T (p.Gln694Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400033218

gnomAD: N/A

Case13: Patient ID M, Female, 15 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Patient L is related to patient M (See Table 1; very minimal information)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000225, HP:0004406

(Easy bruising, gingival bleeding, recurrent epistaxis

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000967, HP:0000979, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, GI bleeding, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dental, hemorrhage after trauma, ear bleeding, hematoma

ProteinExpression: N/A

PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin

CasePreviousTesting: Exon PCR was used to amplify coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.

Gene: ITGB3

Variant: NC_000017.11:g.47284509T>G (p.Leu143Trp)

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

gnomAD: MAF in Other population 0.0001629 http://gnomad.broadinstitute.org/variant/17-45361875-T-G

PreviouslyPublished: PMID: 9376589

PMID: 8317479

Gene: ITGB3

HGNC: 6156

Case1: Gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Lifelong bleeding tendency with prolonged bleeding time

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression:

PlateletAggregation: Absence of in vitro platelet aggregation seen in thrombasthenia (all the information we are provided with)

CasePreviousTesting: RT-PCR on total RNA extracted from the patient's platelets followed by direct sequencing of die PCR products using GPIIb and GPIIIa primers described elsewhere

Gene: ITGB3

Variant: (p.Arg240Trp)

LegacyVariant: (p.Arg214Trp)

ClinVar: 13555

CAiD: CA123228

gnomAD: MAF in the East Asian population is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45363729-C-T

PreviouslyPublished: PMID: 3818957 and Reference 10 in this article

PMID: 7509233

Gene: ITGB3

HGNC: 6156

PMID: 11897046

Gene: ITGB3

HGNC: 6156

Case1: (Patient RM), Male, 73 years old, from Southwest of France

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Other family members were his mother (M.M), his son (J.M.M), and his sister (A.M)

ParentalGenotype: Mother is heterozygous for the mutation

CasePresentingHPOs: HP:0000421 (Epistaxis)

CaseHPOFreeText: Life-long history of mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Flow cytometric analysis shows a reduced aIIbb3 expression in the platelets of the proband and other family members (See Fig. 6)

Platelet Aggregation: Absent platelet aggregation in response to ADP, collagen, arachidonic acid and thrombin receptor activated peptide. Ristocetin induced platelet agglutination was normal

CasePreviousTesting: Screening of the aIIb and b3 genes by PCR-SSCP revealed aheterozygous mutation at position 685 in exon 5 of the b3 gene leading to a 1 96Leu to Pro substitution.

Gene: ITGB3

Variant: NM_000212.2:c.665T>C (p.Leu6656Pro)

LegacyVariant: (p.Leu196Pro)

ClinVar: N/A

CAiD: CA291224887

gnomAD MAF in the European (non-Finnish) population is 0.00006482 https://gnomad.broadinstitute.org/variant/17-45363676-T-C

PMID: 9065456

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions variants in ITGA2B and/or ITGB3; however, no specific GT probands are mentioned harboring these variants mentioned therefore there is insufficient evidence

Case1: Patient PDJ (found in GT database as well) 57 years old, ethnicity not specified

DiseaseAssertion: Thrombocytopenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Quantitative analysis of GPllb-llla surface expression showed only 20,000 GPllb-llla receptors/platelet, approximately half of the value obtained with control platelets

PlateletAggregation: N/A

CasePreviousTesting: DNA sequence analysis of the GPIIIa gene was performed

Gene: ITGB3

Variant: NM_000212.2:c.709_710del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623029

gnomAD: MAF in the European (non-Finnish) population is 0.00001796 https://gnomad.broadinstitute.org/variant/17-45363717-CAG-C

Case#: HS, 1 year old, female

FamilyInfo: Family H, consanguineous Algerian family, with the parents being first cousins. Pedigree is shown in Figure 3.

ParentalGenotype: mother and father both heterozygous for mutation. Proband's sister is also heterozygous.

PlateletAggregation: proband presented defective platelet aggregation to adenosine diphosphate and collagen in a context of epistaxis and bleeding tendency. no mention of ristocetin.

CaseHPOFreeText: propositus HS was diagnosed as type I GT because her platelets were deficient in GPIIb and GPIIIa both on the platelet surface and in α-granules and had undetectable levels of intragranular fibrinogen as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and periodic acid schiff (PAS) staining, Western blot, crossed immuno-electrophoresis, and Scatchard analysis.13 Moreover, the patient developed an iso-immunization directed against GPIIb-IIIa after the first platelet transfusion.

ProteinExpression:

CasePreviousTesting: Mutation was detected by SSCP, followed by direct sequencing.

Gene: ITGB3

Variant: NM_000212.3(ITGB3):c.1053_1058del (p.Ile351_Gly353delinsMet). "sequencing of exon 7 showed a 6-nucleotide deletion resulting in the substitution of Ile325Pro326Gly327 by a Met"

CAID: CA915940648

gnomAD: This variant is absent from gnomAD v2.1.1

PMID: 9226167

Gene: ITGB3

NM_000212:c.2112delC

Case40: (GT-50) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT49-GT52 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Case9: (GT-11) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT12 -GT14 are related to GT-11 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Moderate (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.727G>C (p.Asp243His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case16: (GT-18) Female, carrier status, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-18 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available on bleeding phenotype/severity (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.727G>C (p.Asp243His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case55: (GT-74) Male, age, or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not given (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.437T>C (p.Leu146Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400021960

gnomAD: N/A

Case29: (GT-34) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available for this proband (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Case20: (GT-22) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT-22 is related to GT-21 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Severe (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2302-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034626

gnomAD: N/A

Case49: (GT-60) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

PMID: 30792900

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156 respectively as shown above

Case48: (GT-59) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.

Gene: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T