Case2: P2, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions all patients have a severe bleeding phenotype

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: αIIbβ3 expression levels were (4% in patient 2)

PlateletAggregation: N/A

CasePreviousTesting: Acknowledgements section mentions acknowledging the Genoscope team for sequencing both ITGA2B and ITGB3 genes of the GT patients in this article

Gene: ITGA2B

Variant: NM_000419.3:c.91del (p.Ala31ProsfsX2)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913203486

gnomAD: N/A

Supplementary Table S1:

Case36: GT42, Canadian/Egypt, 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: ITGA2B

Variant: NM_000419.3:c.2148dup (p.Leu717AlafsTer3)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940304

gnomAD: N/A

Supplementary Table S1:

Case42: GT49, French/Spanish, 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: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480SerfsTer106) and NM_000419.3:c.2113T>C (p.Cys705Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA8602816

gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G for the (p.Cys705Arg) variant

Supplementary Table S1:

Case24: GT27, French, gender and age were not specified here

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: ITGA2B

Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and NM_000419.3:c.2468G>A (p.Gly823Glu)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950376 and CA399795351

gnomAD: MAF in the European (non-Finnish) population is 0.000008791 for (p.Tyr471Ter) MAF in the African population is 0.000 for p.Gly823Glu) https://gnomad.broadinstitute.org/variant/17-42453334-C-T

Supplementary Table S1:

Case40: GT47, 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: ITGA2B

Variant: NM_000419.3:c.832del (p.Asp278IlefsTer101)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940374

gnomAD: N/A

Supplementary Table S1:

Case34: GT40, Canadian/Pakistani, 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: ITGA2B

Variant: NM_000419.3:c.857T>A (p.Val286Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805011

gnomAD: N/A

Supplementary Table S1:

Case55: GT65, 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: ITGA2B

Variant: NM_000419.3:c.574+1G>A and NM_000419.3:c.1946+3G>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805691 and CA626121071

gnomAD: MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A

Supplementary Table S1:

Case13: GT14, French, gender age and ethnicity 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: ITGA2B

Variant: NM_000419.3:c.423G>T (p.Trp141Cys) and NM_000419.3:c.2902del (p.Tyr968Metfs*163)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806022 and CA915940332

gnomAD: N/A

Supplementary Table S1:

Case9: French/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: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.3077G>A (p.Arg1026Gln)

LegacyVariant: N/A

ClinVar: 50232

CAiD: CA913184940 and CA10575572

gnomAD: MAF in the European (non-Finnish) population is 0.000008801 https://gnomad.broadinstitute.org/variant/17-42449775-C-T for (p.Arg1026Gln)

Case4: Male (elderly), age not specified, France

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: N/A

Platelet Aggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.2348+5G>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290947484

gnomAD N/A

PreviouslyPublished: 25728920

PMID: 15670032

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a patient with GT; however, the patient does not have variants in ITGA2B and/or ITGB3

PMID: 7525851

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

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

Case3: Patient MR, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.

Gene: ITGA2B and ITGB3

Variant: NM_000419.3:c.526C>G (p.Pro176Ala) and NM_000212.2:c.224del ,

LegacyVariant: (p.Pro145Ala)

ClinVar: N/A

CAiD: CA399805793 and CA8622899

gnomAD: MAF in the European non Fin pop is 0.000008795 for the ITGB3 variant

PMID: 12083483

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

Created page notes for proband information because the table will not let me highlight the proband info

Case10: Patient PL, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.

Gene: ITGA2B

Variant: NM_000419.3:c.1742C>A (p.Ala581Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802112

gnomAD: N/A

Case15: Patient CE, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.

Gene: ITGA2B

Variant: NM_000419.3:c.2113T>C (p.Cys705Arg)

LegacyVariant: (p.Arg674Arg)

ClinVar: N/A

CAiD: CA8602816

gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G

Case2: Female, 65 years old, Iraqi-Jewish origin

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Her brother is the other proband in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000225, HP:0031364, HP:0002249

(Gingival bleeding, epistaxis, ecchymosis, melena)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Surface expression GPIIb/IIIa was 11% of normal

PlateletAggregation: Platelet aggregation in response to thrombin, collagen, ADP and epinephrine was absent, whereas ristocetin induced aggregation was normal

CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the GPIIb gene were amplified by PCR

Gene: ITGA2B

Variant: NM_000419.3:c.1947-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801096

gnomAD: N/A

Case4: 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:0002105, HP:0031364

(Epistaxis, hemoptysis, ecchymosis)

CaseHPOFreeText: Intracranial at birth, haematemesis, haematuria

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation:

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.2473_2478delinsTCACCAGGGCCTTCACCTCAGCATCCACC

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940595

gnomAD: N/A

PreviouslyPublished: 7529063

Case17: Female, Arab, 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:0000132)

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia, melena)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.409-2_419del

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case15: Male, Arab, 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

(Epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.409-2_419del

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case1: Male, 52 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: One of the patient’s daughters carried the c.2437C>A mutation. The other daughter carried the c.1771_1772insG along with c.339C>G mutation, indicating that these mutations are on the same allele.

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Recurrent hemorrhagic symptoms, bleeding time >20 minutes and PFA-100 closure times were > 300 seconds

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Flow cytometric analysis showed a clearly detectable but strongly reduced amount of surface expressed GPIIb and GPIIIa

PlateletAggregation: Platelets failed to aggregate in response to ADP, arachidonic acid, epinephrine, and collagen.

CasePreviousTesting: Sequencing of exons of GPIIb gene was performed

Gene: ITGA2B

Variant: NM_000419.3:c.1771dup (p.Asp560GlyfsX16), NM_000419.3:c.2437C>A (p.His782Asn)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940334, CA399795907, CA500624465

gnomAD: N/A

Case#: Patient ID 2, Female 13 years old. North Indian

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0031364, HP:0003540, HP:0000421, HP:0002239, HP:0000132

Ecchymosis, Impaired platelet aggregation, Epistaxis, Gastrointestinal hemorrhage, Menorrhagia

PlateletAgreggation: LTA with ADP, Epi, Coll, AA, and Ristocetin: Impaired with all agonists

GenotypingMethod: Next generation sequencing. Sanger sequencing used to confirm pathogenic variants

ClinVar: 953042

CAID: CA399804619

Variant: NM_000419.5:c.1028T>C

GnomAD: Not Found

ExpressionEvidence: Flow Cytometry for platelet expression of GPIIb/IIIa in CD41a 4.9% and CD61 96%.

Case#: Patient ID 4, Female 11 years old. North Indian

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0031364, HP:0003540, HP:0000421, HP:0000225

Ecchymosis, Impaired platelet aggregation, Epistaxis, Gingival bleeding

PlateletAgreggation: LTA with ADP, Epi, Coll, AA, and Ristocetin: Impaired with all & aggregation–disaggregation pattern with Ristocetin

GenotypingMethod: Next generation sequencing. Sanger sequencing used to confirm pathogenic variants

FamilyInfo:Father heterozygous c.1186G > A variant; d Mother carrier for c.3092delT variant

Allele 1:

ClinVar: 627218

CAID: CA399804315

Variant:NM_000419.5:c.1186G>A

GnomAD:South Asian at rate of 0.00006622 (2/30202)

Allele 2:

ClinVar:1691488

CAID: CA915940323

Variant: NM_000419.5:c.3092del

GnomAD: NA

ExpressionEvidence: Flow Cytometry for platelet expression of GPIIb/IIIa in CD41a 0% and CD61 15%.

Case8: Male, 31 years old, Tamil Nadu India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967, HP:0000225, HP:0006298

(Epistaxis, ecchymosis, petechiae, gingival bleeding, prolonged bleeding after tooth extraction

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.2236G>T (p.Glu746Ter)

LegacyVariant: (p.Glu715Ter)

ClinVar: N/A

CAiD: CA399798321

gnomAD: N/A

Case6: Male, 14 years old, Tamil Nadu India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0006298, HP:0000967

(Gingival bleeding, prolonged bleeding after tooth extraction, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1651C>T (p.Arg551Trp)

LegacyVariant: (p.Arg520Trp)

ClinVar: N/A

CAiD: CA399802348

gnomAD: MAF in the East Asian population is 0.00005045https://gnomad.broadinstitute.org/variant/17-42457471-G-A

PMID: 2010551

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: 12506038

Gene: ITGA2B

HGNC: 6138

Case1: Female, 21 years old, Japanese (Named Osaka-12 in this study)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The substitution was inherited from her father. The molecular genetic defect inherited from her mother remains determined.

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate mucocutaneous bleeding in childhood

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed revealed a significant reduction in the expression of αIIbβ3 on Osaka-12 platelets

PlateletAggregation: Absent platelet aggregation in response to ADP, epinephrine, and collagen but a normal response to ristocetin

CasePreviousTesting: To identify the molecular genetic defect for the proband of interest, all coding regions of ITGA2B and ITGB3 cDNA amplified by RT-PCR were analyzed

Gene: ITGA2B

Variant: NM_000419.3:c.520T>C (p.Tyr174His)

LegacyVariant: (p.Tyr143His)

ClinVar: N/A

CAiD: CA399805805

gnomAD: N/A

PMID: 1912663

Gene: N/A

HGNC: N/A

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

PMID: 8485050

Gene: ITGA2B

HGNC: 6138

Case9: Patient LM (can be found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A Not reported for this proband

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Undetectable for this patient

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1346G>A (p.Gly449Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399803552

gnomAD: N/A

PreviouslyPublished: Reference number 20 in this article

Case22: Patient AP, gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0006298

(Epistaxis, gingival bleeding, prolonged bleeding after tooth extraction)

CaseHPOFreeText: Hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 12-20% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.3077G>A (p.Arg1026Gln) other mutation was not found

LegacyVariant: N/A

ClinVar: 50232

CAiD: CA10575572

gnomAD: MAF in the European (non-Finnish) population is 0.000008801 https://gnomad.broadinstitute.org/variant/17-42449775-C-T

PreviouslyPublished: References 37 and 38

Case11: Patient Gypsy (found in the GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Blood transfusions required

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Decreased surface expression of GPIIIa and GPIIb

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

PreviouslyPublished: Reference number 22 in this article

Case1: Patient KW (this patient can be found in the GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseHPOFreeText: Blood transfusions needed

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Surface expression of GPIIb/GPIIIa not reported for this patient

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: 4.5-KB DEL, EX2-9

LegacyVariant: N/A

ClinVar: 2890

CAiD: N/A

gnomAD: N/A

PreviouslyPublished: PMID: 1702098

Case9: GT-9, Caucasian, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.1186G>A heterozygous and Father: c.3060_2T>C heterozygous

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.1186G>A and NM_000419.3:c.3060+2T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804315 and CA290944108

gnomAD: MAF in the South Asian population is 0.00006622 http://gnomad.broadinstitute.org/variant/17-42460885-C-T and MAF in the European non-Finnish population is 0.00003876 http://gnomad.broadinstitute.org/variant/17-42451720-A-G

Case11: GT-11, Arab, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.3092delT heterozygous and Father: deceased

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.641T>C and NM_000419.3:c.3092delT

LegacyVariant: N/A

ClinVar: 2901

CAiD: CA115848 and CA915940323

gnomAD: N/A

Case13: GT-13, Swiss, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are moderate (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.555T>G and NM_000419.3:c.1882C>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805736 and CA399801310

gnomAD: MAF in the Latino population is 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A

Case3: GT-3, Turkish, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGB3

Variant: NM_000419.3:c.310+3_310+6del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940325

gnomAD: N/A

Case6: Patient M6, Female, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case2: Patient M2, Female, French Gypsy, age is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Figure 2 for pedigree

ParentalGenotype: Unaffected parents see pedigree Fig 2

CasePresentingHPOs: N/A

CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)

PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case55: GT55, Female, 28, Argentinian/Brazilian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has an affected sister (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000421

(Gingival bleeding, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 11-22% 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.647C>T (p.Ala216Val)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805506

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case35: GT36c, Female, 47 years old, Spanish

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is proband 36 a and affected brother proband 36b

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000132, HP:0011891

(Menorrhagia, post-partum hemorrhage)

CaseHPOFreeText: Intra-abdominal hemorrhage and bleeding after trauma

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.131G>T (p.Gly44Val) and NM_000419.3:c.1440-13_1440-1de (p.Arg480Serfs*106)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806881 and CA913184940

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case7: GT8, Male, 82 at death, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0002239

(Easy bruising, epistaxis, GI bleeding

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 10-15% 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.2348+5G>C (p.Ser756Gly783delInsArg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290947484

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case47: GT47, Male, 11 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe mucocutaneous 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: ITGA2B

Variant: NM_000419.3:c.832del (p.Asp278Ilefs*101)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940374

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case12: GT13, Female, 14, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967 (Petechiae)

CaseHPOFreeText: Moderate bleeding syndrome

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: ITGA2B

Variant: NM_000419.3:c.682C>T (p.Gln228Ter) and NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA399805421 and CA115834

gnomAD: MAF in the East Asian population is 0.0002176 http://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case68: GT72, Female, 56 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000225, HP:0000132, HP:0002239, HP:0006298

(Epistaxis, ecchymosis, gingival bleeding, menorrhagia, GI bleeding, prolonged bleeding after dental extraction)

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.2951C>A (P.Thr984Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399790180

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case52: GT52, Male, 24 years old, Argentenian/Brazil

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Hematomas

(Proband's symptoms decreased during adolescence)

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.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case40: GT41a, Female, 15 years old, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother is proband 41b in this study (See Supplemental Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406, HP:0000978

(Recurrent epistaxis, easy bruising)

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.91del (p.Ala31Profs2) and NM_000419.3:c.2915dup (p.Leu973Alafs63)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913203486 and CA8602531

gnomAD: MAF in the East Asian population is 0.0001088 http://gnomad.broadinstitute.org/variant/17-42452054-C-CG

Supplementary Table S1 & S2 Proband and Variant Information:

Case37: GT39a, Female, 23 years old, Swedish/American

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 39b in this study (See Supplemental Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0006298, HP:0000132

(Bruising susceptibility, epistaxis, prolonged bleeding after dental extraction, menorrhagia)

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.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

gnomAD: MAF in the Latino population 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case38: GT39b, Male, 18 years old, Swedish/American

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is proband 39a in this study (See Supplemental Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0006

(Bruising susceptibility, epistaxis)

CaseHPOFreeText: Hematomas after minor trauma

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.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

gnomAD: MAF in the Latino population 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case14: GT15, Female, 35, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000967, HP:0000421, HP:0000225

(Ecchymosis, petechiae, epistaxis, gingival bleeding)

CaseHPOFreeText: Bleeding from birth and hematomas from excersize

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: ITGA2B

Variant: NM_000419.3:c.2095-19T>A and NM_000419.3:c.2770C>T (p.Gln924Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940312 and CA399792054

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case21: GT24, Female, 45, French (Gypsy)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000132

(Epistaxis, menorrhagia)

CaseHPOFreeText: Post-traumatic hematoma

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.1544+1G>A (p.Val513Leufs*71)

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

PMID: 25728920

Genes: ITGA2B and ITGB3

HGNC: 6138 and 6156

Note: In the annotations, case #'s don't always match up with the exact proband #, because not all probands had GT variants identified in them

Supplementary Table S1 & S2 Proband and Variant Information:

Case15: GT18, Male, 20, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000978

(Ecchymosis, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Residual platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1201G>T (pGly401Cys) andNM_000419.3:c.2800G>T (p.Val934Phe)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804280 and CA290946484

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case46: GT45, Male, 86 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0002239

(Epistaxis, gingival bleeding, 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.551_626del (p.Arg184_Gln208del) and LR deletion

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940373

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case45: GT44, Female, 10 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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.1357C>T (p.Arg453Ter)

LegacyVariant: N/A

ClinVar: 631773

CAiD: CA399803529

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case23: GT26, Male, 45, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978

(Epistaxis, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Much reduced platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His)

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

PMID: 29951177

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: Article mentions Glanzmann thrombasthenia probands; however, no variants associated with patients therefore insufficient evidence

PMID: 16178914

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions various probands with GT; however, there are no mentioned variants in ITGA2B and/or ITGB3, therefore, we have insufficient evidence

Case12: No assertion made on age, gender or ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The identified variants were heterozygote in parents.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1071dup (p.Arg358AlafsTer47)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940225

gnomAD: N/A

Case10: Patient WC, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries

Gene: ITGA2B

Variant: c.2232Gins (Noting this as an Unknown Variant as this won't show up in CAR-- I am sure there is a way to retrieve the CAiD; however, will need to discuss with senior biorcurator)

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

Case19: Patient SB, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries

Gene: ITGA2B

Variant: NM_000419.3:c.3062T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399787956

gnomAD: N/A

Case5: Patient HM, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries

Gene: ITGA2B

Variant: NM_000419.3:c.1878G>C

LegacyVariant: N/A

ClinVar: 2903

CAiD: CA115852

gnomAD: N/A

Case13: Patient TG, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries

Gene: ITGA2B

Variant: NM_000419.3:c.3060G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500261104

gnomAD: N/A

Case1: V.17, Male, French (Gypsy), age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Pedigree shown in Fig 1

ParentalGenotype: Mother and father are heterozygous for the mutation

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The alphaIIb full length cDNA of this patient were amplified by PCR

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

PMID: 23710629

Genes: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: Mention of proband with Glanzmann thrombasthenia however no variants in the proband are mentioned for ITGA2B and ITGB3

Case2: Patient 2, diagnosed at 5 years, gender and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000790

(Epistaxis, gingival bleeding, hematuria)

CaseHPOFreeText: Reduced clot retraction

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Immunoblot analysis of platelet lysates showed no detectable pro-αIIb or mature αIIb in any of the patient samples. Trace amounts of Beta3 were detected in samples from this patient

PlateletAggregation: Absent in vitro platelet aggregation in response to ADP, epinephrine and collagen but a normal initial phase response to ristocetin

CasePreviousTesting: Polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and DNA sequencing was performed for ITGA2B

Gene: ITGA2B

Variant: NM_000419.3:c.953C>G (p.Ser318Leu)

LegacyVariant: p.Ser287Leu

ClinVar: N/A

CAiD: CA399804788

gnomAD: N/A

PMID: 21029361

Gene: ITGA2B

HGNC: 6138

Note: Although article mention 4 probands being studied, the caption under Fig 1 with the pedigree states, "Shown are three of the four homozygous patients (lanes 2, 4 and 6), heterozygotes" therefore the 4th proband is not mentioned

Case1: Male, Israeli-Arab, (age is either 10 or 14)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1C for pedigree

ParentalGenotype: See Fig 1C for pedigree

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967

(Severe epistaxis, ecchymosis, petechiae)

CaseHPOFreeText: Decline of hemoglobin levels to 5 g dl each time epistaxis occurred

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: No surface expression of αIIbβ3 was found in patients’ platelets (See Fig 3)

PlateletAggregation: N/A

CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the aIIb and B3 genes were amplified by PCR using primers

Gene: ITGA2B

Variant: NM_000419.3:c.97A>G (p.Asn2Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806951

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case7: GT7, Female, 31 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, HP:0000132

(Bruising, purpura, ecchymosis, epistaxis, menorrhagia)

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: ITGA2B

Variant: NM_000419.3:c.1652G>A (p.Arg551Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986 (p.Arg551Gln)

gnomAD: MAF in South Asian population: 0.00006536 https://gnomad.broadinstitute.org/variant/17-42457470-C-T

Supplementary Tables 1 and 2 combined information:

Case5: GT5, Female, 25 years old; however, now deceased

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000132, HP:0000421, HP:0002239, HP:0002170

(Menorrhagia, epistaxis, gastrointestinal bleeding, intracranial hemorrhage)

CaseHPOFreeText: Post traumatic hemorrhage

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: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.2159T>C (p.Leu720Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA115834 (p.Arg584Ter) and CA399798955 (p.Leu720Pro)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case2: GT2, Male, 13 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not 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: ITGA2B

Variant: NM_000419.3: c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

gnomAD: MAF in East Asian population: 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Tables 1 and 2 combined information:

Case30: GT30, Female, 13

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225, HP:0000132

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

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: ITGA2B

Variant: NM_000419.3:c.2330C>A (p.Ala777Asp) and NM_000419.3:c.2602-3C>G (no protein notation given)

LegacyVariant: N/A

ClinVar: 2893 (c.2602-3C>G)

CAiD: CA399796685 (p.Ala777Asp) and CA10575472 (c.2602-3C>G)

gnomAD: MAF for East Asian population: 0.00006523 https://gnomad.broadinstitute.org/variant/17-42453087-G-C

Supplementary Tables 1 and 2 combined information:

Case17a: GT17a, Female, 14 years old, sister of GT17b proband

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per supplementary table 1

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

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

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: Post traumatic hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed <5% 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: ITGA2B

Variant: NM_000419.3:c.799+2T>C and NM_000419.3:c.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805155 (c.799 +2 T>C) and CA8602626 (p.Gln891Ter)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case37: GT37, Female, 1 year old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

(Bruising, purpura, ecchymosis)

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: ITGA2B

Variant: NM_000419.3:c.1993C>T (p.Gln665Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801004

gnomAD: MAF in East Asian population: 0.00005461 https://gnomad.broadinstitute.org/variant/17-42455831-G-A

Supplementary Tables 1 and 2 combined information:

Case19: GT19, Female, 32 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per Table 1.

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000790, HP:0000132

(Epistaxis, gingival bleeding, hematuria, menorrhagia)

CaseHPOFreeText: Post traumatic hemorrhage

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: ITGA2B

Variant: NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: N/A

ClinVar: 381748

CAiD: CA8603182 (p.Gly412Arg)

gnomAD: MAF in Latino population: 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

Case#: patient 1

DiseaseAssertion: Glanzmann thrombasthenia

**FamilyInfo: **

ParentalGenotype: If noted by authors, annotate with the carrier status of each parent in regards to the variant(s) identified in the proband.

CasePresentingHPOs:

PlateletAggregation: absent platelet integrin αIIbβ3. Monolayer of spread platelets essentially devoid of fibrinogen binding but with high CD62P expression and phosphatidylserine exposure (Figure S1). Figure 5.

CaseHPOFreeText:

CaseNotHPOs:

**CaseNotHPOFreeText: **

ProteinExpression:

CasePreviousTesting:

**PreviouslyPublished: **

Gene: ITGA2B

**HGVS: ** NM_000419.4:c.2943G>A

**ClinVar: **

CAID: CA500262444

**gnomAD: **

PMID: 10029591

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a case report of a GT patient in another article; however, this article does not specifically mention any GT case reports

PreviouslyPublished: PMID: 2180491 and PMID:

PMID: 15293575

Gene: ITGA2B

HGNC: 6138

PMID: 8925838

Gene: ITGA2B

HGNC: 6138

Case11: (M3) Female, 12 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case20: (M12) Female, 39 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case13: (M5) Male, 9 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case19: (M11), Male, 63 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case8: (GT-8) Female, 10 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: <5% surface expression levels of αIIbβ3

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.682C>T (p.Gln228Ter) and NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: (p.Gln197Ter) and (p.Arg558Ter) (The paper gives legacy and current nomenclature)

ClinVar: 2892 (p.Arg584Ter)

CAiD: CA399805421 (p.Gln228Ter) CA115834 (p.Arg584Ter)

gnomAD MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

Case10: (M2) Female, 4 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Supplemental Table S1:

Cases38and39: Females, Italy, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)

CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed

Gene: ITGA2B

Variant: NM_000419.3:c.2254C>G (p.Leu752Val) and NM_000419.3:c.2264G>C (p.Arg755Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602773 and CA8602772

gnomAD: MAF in the European non Finnish population is 0.00001032 https://gnomad.broadinstitute.org/variant/17-42454390-G-C and MAF in the European non Finnish population is 0.00001060 https://gnomad.broadinstitute.org/variant/17-42454380-C-G

PreviouslyPublished: PMID: 12083483

Supplemental Table S1:

Case2: Female, India, age not specified

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: Absent platelet aggregation (all the information that is provided in Supp. Table S1)

CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed

Gene: ITGA2B

Variant: NM_000419.3:c.1520C>G (p.Pro507Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802643

gnomAD: N/A

PreviouslyPublished: PMID: 16463284

Supplemental Table S1:

Case4: Male, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia