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

Case14: 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

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia)

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

Case16: 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: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 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

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

Case24: 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:0031364, HP:0000132

(Epistaxis, ecchymosis, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case10: 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, HP:0002239, HP:0002573

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

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

Case12: 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, HP:0002249

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

CaseHPOFreeText: Retroperitoneal, 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

Case18: 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:0031364

(Epistaxis, ecchymosis)

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

Case8: 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, HP:0002573

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

CaseHPOFreeText: Haemarthrosis, retro-peritoneal 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

Case22: 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)

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia)

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

Case11: 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, HP:0002249

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

CaseHPOFreeText: Colon angiodysplasia, retroperitoneal, haematuria, haemarthrosis

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

Case1: 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: N/A

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: 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

Case21: 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: 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.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

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

Case2: 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:0002249

(Epistaxis, gingival bleeding, menorrhagia, melena)

CaseHPOFreeText: Petechial rash, post-partum bleeding, colon angiodysplasia, haematemesis

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

Case23: 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:0000132)

(Epistaxis, menorrhagia)

CaseHPOFreeText: Haematuria

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

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:

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:

Case25: GT28, Male, 36, French/Syrian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister (See Supplemental Table 1)

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 5-10% 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: "LR Dup" (See Supplementary Table 1)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case34: GT36b, Male, 60 years old, Spanish

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sisters who are proband 36a and 36c in this study

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406

(Recurrent epistaxis)

CaseHPOFreeText: Embolism of the submaxillary artery

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:

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:

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:

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:

Case4: GT5, Male, 7, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 brother, that is all Supp table S1 states

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978, HP:0002138

(Epistaxis, easy bruising, subararachnoid hemorrhoid)

CaseHPOFreeText: Post-traumatic bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669 and CA8623443

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

Case41: GT41b, Male, 13 years old, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 41a in this study (See Supplemental Table S1)

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: 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:

Case33: GT36a, Female, 49 years old, Spanish

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 36b and affected sister who is proband 36c in this study

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseHPOFreeText: Bleeding at the 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: 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:

Case26: GT30, Female, age not specified, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother (See Supplementary Table 1)

ParentalGenotype: N/A

CasePresentingHPOs:

(Epistaxis, GI bleeding)

CaseHPOFreeText: Diffuse bruising mainly with trauma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 5-10% 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.777+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623036

gnomAD: MAF in the Latino population is 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-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:

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:

Case28: GT33a, Male, age not specified, USA/Laos

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is proband 33b 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:

Case60: GT62, Female, 58 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister (that is all the information we are given)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000225, HP:0000132, HP:0006298

(Easy bruising, gingival bleeding, menorrhagia, bleeding after dental extraction)

CaseHPOFreeText: Esophageal 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.31T>C (p.Trp11Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291240306

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case31: GT35a, Female, 18 years old, USA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is 35 b 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:

Case64: GT67, Male, 61 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is now dead (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs:

(Gingival bleeding, epistaxis, 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.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.1618C>T (p.Gln540Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA399802411

gnomAD: MAF in the African population is 0.000 https://gnomad.broadinstitute.org/variant/17-42457504-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967, HP:0030137

(Epistaxis, purpura, ecchymosis, petechiae, prolonged bleeding at circumcision)

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:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967

(Epistaxis, purpura, ecchymosis, petechiae)

CaseHPOFreeText: Lots of bleeding at circumcision

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

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

Case12: Patient ID L, Female, 10 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

(Easy bruising, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000967, HP:0000979, HP:0004406, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, recurrent epistaxis, 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

Case11: Patient ID K, Male, 5 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Related to Patient's I and J (See Table 1)

ParentalGenotype: N/A (Parents are consangenous)

CasePresentingHPOs: HP:0000978, HP:0004406, HP:0000225, HP:0002239, HP:0000790

(Easy bruising, recurrent epistaxis, gingival bleeding, GI bleeding, hematuria)

CaseHPOFreeText: Hemorrhage after trauma, hematoma, ear bleeding

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

(Petechiae, purpura, intracranial hemorrhage, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dental, ear bleeding

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: ITGA2B

Variant: NM_000419.3:c.1652G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

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

PreviouslyPublished: PMID: 19172520

Case10: Patient ID J, Female, 5 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Related to Patient's I and K (See Table 1)

ParentalGenotype: N/A (Parents are consangenous)

CasePresentingHPOs: HP:0000978, HP:0004406, HP:0000225, HP:0002239

(Easy bruising, recurrent epistaxis, gingival bleeding, GI bleeding

CaseHPOFreeText: Hemorrhage after trauma, hematoma

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

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

CaseNotHPOsFreeText: Hemorrhage after dental, ear bleeding

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: ITGA2B

Variant: NM_000419.3:c.1652G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

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

PreviouslyPublished: PMID: 19172520

Case9: Patient ID I, Female, 3 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Related to Patient's J and K (See Table 1)

ParentalGenotype: N/A (Parents are consangenous)

CasePresentingHPOs: HP:0000967, HP:0000979, HP:0000978, HP:0004406

(Petechiae, purpura, easy bruising, recurrent epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000225, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Gingival bleeding, GI bleeding, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dnetal, 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: ITGA2B

Variant: NM_000419.3:c.1652G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

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

PreviouslyPublished: PMID: 19172520

Case9: No assertion made on age, gender or ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The identified variants were heterozygote in parents.

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

(Easy bruising, menorrhagia, epistaxis, purpura)

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.189_236del (c.189-319_236del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940231

gnomAD: N/A

Case1: Male, 40 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Mild bleeding symptoms have been reported in his grandmother and a first cousin, but they were not available for further study

ParentalGenotype: The mother is asymptomatic; however, genetic testing confirmed her to be heterozygous for the GT mutation (No information on father's genetic information for this mutation)

CasePresentingHPOs: HP:0000225

(Gingival bleeding)

CaseHPOFreeText: Very mind bleeding

CaseNotHPOs: HP:0000421, HP:0000978

(Epistaxis, bruising)

CaseNotHPOsFreeText: N/A

ProteinExpression: The surface expression of GPIIb-IIIa was about 20% of normal, whereas GPIb (93%) was normally expressed (See Figure 1A)

PlateletAggregation: Platelet aggregation was markedly impaired in response to physical agonists including: ADP, arachidonic acid, epinephrine, and collagen; however, ristocetin induced normal aggregation

CasePreviousTesting: All 30 exons and immediate flanking sequences of the GPIIb gene, and all 15 exons and immediate flanking sequences of the GPIIIa gene, were amplified by PCR.

Gene: ITGB3

Variant: NM_000212.2:c.1756T>C (p.Cys586Arg)

LegacyVariant: (p.Cys560Arg)

ClinVar: N/A

CAiD: CA400032477

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case16: GT16, Male, 31 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per supplementary table 1; however very minimal information

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 <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.2333A>C (p.Gln778Pro) and NM_000419.3:c.2267+1G>T no protein coding sequence available

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro)

CAiD: CA290947544 (p.Gln778Pro) and CA399798124 for (c.2267+1G>T )

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case18: Gt18, Male, 20 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1; however, very minimal information

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421

(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.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602626 (p.Gln891Ter)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case12: GT12, Male, 10 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family history available per Table 1; however, no further information given

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 10-20% 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.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

Case2: Male, age not specified, Cypriot (father of 3 year old)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Daughter and brother were also affected with same mutation (See Figure 3 for family pedigree)

ParentalGenotype: Parents were heterozygous for same mutation (See Figure 3 pedigree)

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

(Gingival bleeding, epistaxis, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets

PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation

CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.

Gene: ITGA2B

Variant: M_000419.3:c.605T>G (p.Phe202Cys)

LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)

ClinVar: N/A

CAiD: CA399805605

gnomAD: N/A

Case05: (GT-05) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-05 see Table 1

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

CasePresentingHPOs: Bleeding severity: Mild (See Supplementary Table 3)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not 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: ITGA2B

Variant: NM_000419.3:c.1210+5G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case15: (GT-17) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-17 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.727G>C (p.Asp243His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case4: (GT-04) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-04 see Table 1

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not 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: ITGA2B

Variant: NM_000419.3:c.1210+5G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case1: Female, 5 years old, South East Asian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Information given on paternal grandmother

ParentalGenotype: Article mentions that NM_000419.3:c.1946+1G>A was of maternal inheritance and NM_000419.3:c.2944G>A (Val951Met) and NM_000419.3:c.2965G>A (p.Ala958Thr) is of paternal inheritance giving triple heterozygosity

CasePresentingHPOs: HP:0000978, HP:0000421

(Severe bruising, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Flow cytometry showed an ∼4% residual surface expression of αIIbβ

PlateletAggregation: No aggregation in response to ADP, epinephrine or arachidonic acid but a small residual response to collagen

CasePreviousTesting: Extraction of genomic DNA was done and PCR amplification of DNA fragments corresponding to each of the 30 exons in ITGA2B and 15 exons of ITGB3 and SSCP analysis were all performed

Gene: ITGA2B

Variant: NM_000419.3:c.2944G>A (p.Val982Met) and NM_000419.3:c.2965G>A (p.Ala989Thr) and NM_000419.3:c.1946+1G>A

LegacyVariant: (p.Val951Met) and (p.Ala958Thr)

ClinVar: 381747 and 417951 and 569057

CAiD: CA16608466 and CA8602498 and CA8602901

gnomAD: MAF in the Europmean (non-Finnish) population is 0.00006486 https://gnomad.broadinstitute.org/variant/17-42451838-C-T and MAF in the Other population is 0.001939 https://gnomad.broadinstitute.org/variant/17-42451817-C-T and MAF in the East Asian population is 0.00007555 https://gnomad.broadinstitute.org/variant/17-42456010-C-T

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

Case1: Male, 61 years old, Iraqi-Jewish origin

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: His sister 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 9% 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

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

Case1: Female, 33 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Fetus was heterozygous for this mutation

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The GPIIb–IIIa complex was not detectable on the platelets’ surface

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

Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:

Case4: GT-4, age, gender, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed that αIIbβ3 expression was less than 5%

PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.

CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.

Gene: ITGB3

Variant: NM_000212.2:c.569A>G (p.Tyr190Cys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023236

gnomAD: N/A

Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:

Case2: GT-2, age, gender, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Segregation analysis confirmed in presence of heterozygous mutations in this proband.

ParentalGenotype: Although segregation analysis confirmed, we do not know which variant in particular came from mom or dad.

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed that αIIbβ3 expression was less than 5%

PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.

CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.

Gene: ITGA2B

Variant: NM_000419.3:c.2473_2481delinsTCACCTGGTC and NM_000419.3:c.641T>C (p.Leu214Pro)

LegacyVariant: p.Leu183Pro

ClinVar: (p.Leu214Pro is 2901)

CAiD: CA915940289 and CA115848

gnomAD: N/A

Case2: Male, 9 years old, Japanese

DiseaseAssertion: Macrothrombocytopenia

FamilyInfo: Information on mother is given (minimal other family information)

ParentalGenotype: Mother: ITGA2B (Phe993del heterozygous)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Surface expression of αIIbβ3 in platelets of the patient and his mother was about 80% compared to control subjects with an increase of CD42b expression

PlateletAggregation: N/A

CasePreviousTesting: The entire coding sequence of exons and exon-intron boundaries of ITGA2B and ITGB3 and the whole coding regions of ITGA2B and ITGB3 cDNA obtained from platelets were sequenced as previously described. In the case of ITGA2B p.Phe993del, PCR products obtained from amplification of exon 30 of ITGA2B from the patient's DNA were subcloned to pCR2.1-TOPO and sequence analysis was performed

Gene: ITGA2B

Variant: NM_000419.3:c.3070_3072del (p.Phe1024del)

LegacyVariant: p.Phe993del legacy nomenclature

ClinVar: N/A

CAiD: CA8602460

gnomAD: N/A

Case3: Female, 8 years old, Japanese

DiseaseAssertion: Thrombocytopenia

FamilyInfo: Information on mother and grandfather available in Table 1(minimal information on other family members)

ParentalGenotype: Mother: ITGB3 (p.Asp621_Glu660del heterozygous) See Table 1

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: Subaponeurotic hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Surface expression levels of αIIbβ3 in platelets of patient were decreased to around 65% of normal subjects with increase of CD42b (See Table 1)

PlateletAggregation: N/A

CasePreviousTesting: Sequence analysis of DNA revealed the patient's mutation. RT-PCR was also performed. The entire coding sequence of exons and exon-intron boundaries of ITGA2B and ITGB3 and the whole coding regions of ITGA2B and ITGB3 cDNA obtained from platelets were sequenced.

Gene: ITGB3

Variant: NM_000212.2:c.2134+1G>A (p.Asp621_Glu660del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400033344

gnomAD: N/A

Case1: Female, 9 years old, Japanese

DiseaseAssertion: Macrothrombocytopenia

FamilyInfo: Information given in Table 1 and Fig 2

ParentalGenotype: Mother: ITGA2B (p.Arg422Ter heterozygous) and Father: ITGA2B (p.Gly991Cys heterozygous) See Table 1 for this information

Sequencing of parental DNA indicated parental mutations. CasePresentingHPOs: HP:0000979, HP:0000421, HP:0000978

(Purpura, epistaxis, bruising)

CaseHPOFreeText: Hemorrhage after dental

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometric analysis showed that surface αIIbβ3 expression in platelets (was markedly impaired 3-11%)

PlateletAggregation: N/A

CasePreviousTesting: Sequence analysis of entire coding regions of exons and exon-intron boundaries of ITGA2B and ITGB3 gene of the patient revealed two novel mutations in ITGA2B.

Gene: ITGA2B

Variant: NM_000419.3:c.3064G>T (p.Gly1022Cys) and NM_000419.3:c.1357C>T (p.Arg453Ter)

LegacyVariant: (p.Gly991Cys legacy nomenclature for p.Gly1022Cys) and (p.Arg422Ter legacy nomenclature for p.Arg453Ter)

ClinVar: 631773

CAiD: CA399787943 and CA399803529

gnomAD: N/A

Case1: Female, 21 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Blood samples collected from brother, no other information provided

ParentalGenotype: Father heterozygous: NM_000419.3:c.258G>C and mother heterozygous: NM_000419.3:c.2334A>C

CasePresentingHPOs: HP:0000421, HP:0000979

(Epistaxis, purpura)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis and western blot analysis showed a remarkable reduction in aIIb b3 and aIIb, and a moderate reduction in b3 in the platelets of the patient (data not shown)

PlteletAggregation: N/A

CasePreviousTesting: Nucleotide sequences of aIIb cDNA and b3 cDNA amplified by reverse transcription polymerase chain reaction (RT-PCR) were analyzed

Gene: ITGA2B

Variant: NM_000419.3:c.258G>C (p.Leu86Pro) and NM_000419.3:c.2334A>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500624524 and CA399796662

gnomAD: N/A

Case1: Female, 1 year old, ethnicity not specified (patient from Morocco)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Her brother is asymptomatic. Her first cousin, (male) died as a result of some unknown bleeding disorder

ParentalGenotype: Parents fully sequenced and

CasePresentingHPOs: HP:0000967, HP:0000978

(Petechia, bruising)

CaseHPOFreeText: Mucocutaneous hemorrhages

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed less than 10% of ITGA2B and ITGB3 complexes

PlateletAggregation: Platelet aggregation in response to ADP, thrombin, collagen and epinephrine was less than 10% of normal platelets and risotcetin induced platelet agglutination was normal

CasePreviousTesting: Complete analysis of ITGA2B and ITGB3 coding sequences were performed (PCR)

Gene: ITGA2B

Variant: NM_000419.3:c.188G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603528

gnomAD: MAF in the European (non-Finnish) population is 0.000008803 http://gnomad.broadinstitute.org/variant/17-42466654-C-T

Case1: Female, age and ethnicity is previously described in Ruan et al, 1993, but access not available to this article

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: The propositus' twin brother was also affected

ParentalGenotype: Article mentions, "Thus the two affected members are double heterozygote having inherited two different abnormal GPIIb alleles, one from the father and the other from the mother"

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding time > 15 minutes

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Absent or reduced platelet GPIIb and GPIIIa assessed by Western blotting

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

CasePreviousTesting: PCR was used to amplify the defective segment of the GPIIb gene

Gene: ITGA2B

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

LegacyVariant: c.9644C>T

ClinVar: 2892

CAiD: CA115834

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

Case1: Male, French, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Son was heterozygous carriers of the p.Leu196Pro mutation (Sister died from nasal bleeding when she was a child)

ParentalGenotype: Mother is heterozygous for p.Leu196Pro mutation (Father not alive)

CasePresentingHPOs: HP:0000421 (Epistaxis)

CaseHPOFreeText: Lifelong history of mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Expression showed 8% of normal platelet content for αIIbβ3

PlateletAggregation: Absent aggregation to physiologic agonists

CasePreviousTesting: Screened exons and splice sites of ITGB3 and ITGA2B genes of patient by single-strand conformation polymorphism analysis of PCR products.

Gene: ITGB3

Variant: NM_000212.2:c.665T>C (Leu222Pro) and NM_000212.2:c.1871G>A (p.Cys624Tyr)

LegacyVariant: p.Leu196Pro and p.Cys598Tyr

ClinVar: N/A

CAiD: CA291224887 and CA400032726

gnomAD: N/A

Case1: Female, 49 years old, French

DiseaseAssertion: Glanzmann thrombasthenia (diagnosed when 5 years old)

FamilyInfo: A brother died from hemorrhage when he was 4 years old, but an adult sister has never experienced untoward bleeding. (Case History Supp Table 1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0004406, HP:0000132, HP:0000225, HP:0000790

(Easy bruising, recurrent epistaxis, menorrhagia, gingival bleeding, hematuria

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis showed no biding of P2 and AP-2, two MoAbs recognizing alphaIIbBeta3 and a very weak binding of MoAbs to Beta3 to platelets of the proband

PlateletAggregation: Platelet function testing confirmed an absence of aggregation to ADP, collagen, arachidonic acid and thrombin but the response to ristocetin was normal (Case History Supp Table 1)

CasePreviousTesting: Direct sequencing of all exons and splice sites of ITGA2B (30 exons) and ITGB3 (15 exons) was performed by the French National Sequencing Center. Briefly, exons and flanking regions of ITGA2B and ITGB3 were amplified by PCR with a high fidelity Taq polymerase permitting large fragment amplification. PCR fragments were sequenced.

Gene: ITGB3

Variant: (p.Pro189Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

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

Case12: Male, 3 years old, Indian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sibling is proband number 11 in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002249, HP:0000421 (Melena, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Diagnosis of GT was made on the basis of quantitive determination of receptor count by flow cytometric analysis of GPIIb-IIIa

PlateletAggregation: Diagnosis of GT was made on the basis of impaired platelet aggregation (platelet aggregation was tested against ristocetin, ADP, collagen, epinephrine and arachidonic acid)

CasePreviousTesting: Multiplex PCR by using GPIIb primers and CSGE analysis were performed

Gene: ITGA2B

Variant: NM_000419.3:c.1600+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802454

gnomAD: N/A

Case1: Male, 8 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sister had no bleeding tendency (all the information given in the previously published article cited in this annotation)

ParentalGenotype: Parental mutations shown in Fig. 3 A and B

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Tonsilar bleeding

CaseNotHPOs: HP:0000979

(Purpura)

CaseNotHPOFreeText: N/A

ProteinExpression: Western blotting indicated that the proband's platelets contained no normal GPIIb, but showed a trace amount of an abnormal GPIIb (-6% with respect to the GPIIb level in a normal individual).

PlateletAggregation: Decreased aggregation in response to ADP, collagen and epinephrine but a normal ristocetin-induced aggregation (this information was obtained from the previously published article cited at in this annotation)

CasePreviousTesting: Genomic DNA fragments containing exons of the GPIIb gene were amplified by PCR

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.2602-3C>G

LegacyVariant: N/A

ClinVar: 2892 and 2893

CAiD: CA115834 and CA10575472

gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF in the East Asian population is 0.00006523 https://gnomad.broadinstitute.org/variant/17-42453087-G-C

PreviouslyPublished: PMID: 1891767

Case1: (GTa) Female, 27 years old, Irish Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: No family history of bleeding

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978

(Bruising)

CaseHPOFreeText: Excessive bleeding after a normal delivery

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Reduced expression of GPIIb/IIIa

PlateletAggregation: Platelet aggregation to ADP, thrombin receptor activating peptide, thrombin and U46619 was less than 10% and ristocetin induced agglutination was normal

CasePreviousTesting: Total RNA isolated from the proband's platelets was used as a template for RT PCR. Seven primer pairs were used to amplify overlapping regions of the entire GPIIIa coding sequence using cDNA template

Gene: ITGB3

Variant: NM_000212.2:c.655G>A (p.Val219Met)

LegacyVariant: (p.Val193Met)

ClinVar: N/A

CAiD: CA8623016

gnomAD: MAF in the South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45363666-G-A