Case13: (GT-15) Male, carrier, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT16-GT20 are related to GT-15 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 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

Case3: (GT-03) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-03 see Table 1

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: N/A (See Supplemental 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

Case26: (GT-31) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related to GT31

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

Case46: (GT-57) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

Case52: (GT-71) Gender, age, or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

Variant: NM_000419.3:c.1142C>T (p.Thr381Ile)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804396

gnomAD: N/A

Case28: (GT-33) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

Variant: NM_000212.2:c.985A>G (p.Asn329Asp)

LegacyVariant: N/A

ClinVar: 323865

CAiD: CA8623107

gnomAD: MAF in Other population 0.0005534 http://gnomad.broadinstitute.org/variant/17-45367092-A-G

Case44: (GT-54) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

Case25: (GT-30) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT30 is related to GT29

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

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

Case34: (GT-44) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT43-GT44 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

Variant: NM_000419.3:c.1620G>C (p.Gln540His) and NM_000419.3:c.1616T>G (p.Leu539Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802407 and CA399802416

gnomAD: N/A

Case54: (GT-73) Gender, age, or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

Variant: NM_000212.2:c.985A>G (p.Asn329Asp)

LegacyVariant: N/A

ClinVar: 323865

CAiD: CA8623107

gnomAD: MAF in Other population 0.0005534 http://gnomad.broadinstitute.org/variant/17-45367092-A-G

Case21: (GT-25) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT-26 is related to GT-25 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 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: ITGA2B

Variant: NM_000419.3:c.1879-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Case27: (GT-32) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

Case19: (GT-21) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034626

gnomAD: N/A

Case12: (GT-14) Female, carrier, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT11 -GT13 are related to GT-14 see Table 1

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Not available (See Supplementary Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case23: (GT-27) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT28 is related to this proband GT 27; however, no DNA was available for testing for GT28.

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

Variant: NM_000212.2:c.1835G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032647

gnomAD: N/A

Case47: (GT-58) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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.1543del (p.Ser513fs)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500651429

gnomAD: N/A

Supplementary Table S1:

Case52: GT61, French/Italian, gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.224del (p.Cys75LeufsTer10)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: N/A

Supplementary Table S1:

Case45: GT52, Argentina/Brazil, 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.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1:

Case2: GT3, French, age and gender not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.353T>A (p.Leu118His) and NM_000212.2:c.709_710del (p.Ser237Cysfs*13) and NM_000212.2:c.1732G>A (p.Asp578Asn)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224511 (p.Leu118His) and CA8623029 (p.Ser237Cysfs*13) and CA8623343 (p.Asp578Asn)

gnomAD: MAF in the European (non-Finnish) population in (p.Ser237Cysfs*13) is 0.00001796 https://gnomad.broadinstitute.org/variant/17-45363717-CAG-C and MAF in the Other population for (p.Asp578Asn) is 0.0008149 https://gnomad.broadinstitute.org/variant/17-45376715-G-A

Supplementary Table S1:

Case58: GT, French, gender and age are 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.1413C>G (p.Tyr471Ter) and other other variant is stated as "LR deletion" so I will note it as an Unknown Variant

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950376

gnomAD: MAF in the European (non-Finnish) population is 0.000008791 https://gnomad.broadinstitute.org/variant/17-42457994-G-C

Supplementary Table S1:

Case3: GT4, French Gypsy, 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.1544+1G>A (p.Val513Leufs*71)

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Supplementary Table S1:

Case57: GT67, French, gender and age are 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.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:

Case25: GT28, French/Syrian, 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: All the supplemental table says is "LR dup" no other information is provided here (I will note this as Unregistered-please feel free to change this by commenting and letting me know)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Supplementary Table S1:

Case19: GT22, 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.408+11C>A and NM_000419.3:c.1259T>C (p.Va;420Ala)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940333 and CA399803733

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:

Case45: GT53, Argentina/Brazil, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.356G>A (p.Arg119Gln) and NM_000212.2:c.1697G>A (p.Gly566Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622925 and CA400032338

gnomAD: MAF in the African population is 0.0002470 https://gnomad.broadinstitute.org/variant/17-45360910-G-A

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:

Case31: GT38, Sweden/USA, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.79+1G>A and NM_000212.2:c.940-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400028478 and CA400025605

gnomAD: N/A

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:

Case28: GT33a, USA/Laos, gender and age not specified or reported

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Ley705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8623443

gnomAD: MAF in the Other population is 0.0001385 for (p.Arg88Ter) https://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 for (p.Ley705Cysfs*4) https://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1:

Case6: GT7, French, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.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 https://gnomad.broadinstitute.org/variant/17-45360741-C-T

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:

Case60: GT70, French/Arab, gender and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: M_000212.2:c.613_614+2del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940309

gnomAD: N/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)

Case21: (M13) Female, 10 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

Case7: (GT-7) Female, 57 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: ITGB3

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

LegacyVariant: (p.Pro163Ser) (The paper gives legacy and current nomenclature)

ClinVar: N/A

CAiD: CA291224669

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

Case14: (M6) Female, 37 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

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

Case1: (GT1), Male, 60 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding defects

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: ITGB3

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

LegacyVariant: (p.Tyr318Ser) (The paper gives legacy and current nomenclature)

ClinVar: N/A

CAiD: CA400025814

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:

Case37: Female, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mild 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.2264G>C (p.Arg755Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602772

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

PreviouslyPublished: PMID: 19172520

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

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding from multiple sites

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.1651C>T (p.Arg551Trp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

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

PreviouslyPublished: PMID: 16879215

Supplementary Tables 1 and 2 combined information:

Case11: GT11, Female, 12 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:0000225, HP:0000225

(Bruising, purpura, ecchymosis, 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: ITGB3

Variant: NM_000212.2:c.842A>C (p.His281Pro) and NM_000212.2:c.1199G>A (p.Cys400Tyr)

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

CAiD: CA400024802 (p.His281Pro) and CA123244 (p.Cys400Tyr)

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:

Case36: GT36, Male, 8 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, HP:0002239

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

CaseHPOFreeText: Intestinal intrussusception

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1913+5G>T (c.1913+5G>T)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623377

gnomAD: MAF in the East Asian population 0.0001633 https://gnomad.broadinstitute.org/variant/17-45376901-G-T

Supplementary Tables 1 and 2 combined information:

Case27: GT27, Male, 29 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

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

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

(Bruising, purpura, ecchymosis)

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.2333A>C (p.Gln778Pro) This article is not completed-Meera

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: MAF in East Asian population: 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Tables 1 and 2 combined information:

Case10: GT10, Male, 8 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.2236G>T (p.Glu746Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399798321

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case15a: Male, 15 years old, brother to GT15b

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1, brother to GT15b

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Platelet aggregation showed no response to ADP, a small response to collagen but normal response to ristocetin

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case1: GT1, Female, 5 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.1051C>T (p.Arg351Ter) and NM_000419.3:c.2029G>A (p.Glu677Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290954030 (p.Arg351Ter) and CA399800002 (p.Glu677Lys)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case39: GT39, Male, 25 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: HP:0100309 (Subdural hematoma)

CaseHPOFreeText: Post traumatic hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 50-100% (variant) 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.2570G>T (p.Cys857Phe) and NM_000419.3:c.1769G>A (p.Arg590Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399794409 (p.Cys857Phe) and CA8602943 (p.Arg590Gln)

gnomAD: MAF for (p.Arg590Gln) in the Latino population 0.0002314 https://gnomad.broadinstitute.org/variant/17-42457166-C-T

Supplementary Tables 1 and 2 combined information:

Case34: GT34, Male, 3 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,HP:0000225

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

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.432G>A (p.Trp144Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805999

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case14: GT14, Female, 5 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, 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

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

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:

Case28: GT28, Female, 6 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, HP:0000225, HP:0002239

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

CaseHPOFreeText: Post traumatic hemorrhage

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: ITGB3

Variant: NM_000212.2:c.1728del (p.S577Pfs*92) and NM_000212.2:c.892C>T (p.Gln298Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940253 (p.S577Pfs*92) and CA400025098 (p.Gln298Ter)

gnomAD: N/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:

Case25: GT25, Female, 26 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000789,

(Epistaxis, gingival bleeding, menorrhagia, infertility)

CaseHPOFreeText: Rupture of corpus luteum

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1495T>C (p.Cys499Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400029525

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

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

Case14: GT-14, Turkish, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe with pathogenic bleeding time (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.1752+2T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602969

gnomAD: MAF in the European non-Finnish population is 0.000008834 http://gnomad.broadinstitute.org/variant/17-42457368-A-G

Case16: GT-16, Kosovo, gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother: c.1594T>C heterozygous and Father: 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.842C>T and c.2602–2A>G/c.2602–3C>A het do not show up in the clin gen registry (Unregistered Variant?)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805055

gnomAD: N/A

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

CaseHCM147: 31 yrs report, Vietnam, Asian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: Family history of Sudden Cardiac Death and Hypertrophic Cardiomyopathy, Has a 9 year old daughter with the same variant but no symptoms

CasePresentingHPOs: HP:0100749, HP:0006698, HP:0031295 (Chest pain, Dilatation of the ventricular cavity, Left atrial enlargement)

HPOsFreeText: Maximal LV thickness 32 mm

CaseNotHPOs: HP:0005110, HP:0001297, HP:0004756 (Atrial fibrillation, Stroke, Ventricular tachycardia)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The gene panel included 10 sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC1, TNNC1, MYH6), 9 genes encoding Z-disk components and Ca2+ homeostasis factors (LDB3, CSRP3, TCAP, VCL, ACTN2, MYOZ2, NEXN, JPH2, PLN), and 4 genes involved in HCM phenocopies (GLA, LAMP2, PRKAG2, TTR), All probands had left ventricular wall thickness >= 15 mm and no other diseases that can cause secondary hypertrophy

CaseGenotypingMethod: The coding region, flanking sequences, and untranslated regions of each gene were enriched by LC-PCR, amplified, and sequenced on the Illumina MiSeq or MiniSeq platform. Identified variants were then filtered for pathogenicity and confirmed by Sanger sequencing.

Variant: NM_000257.4(MYH7):c.2156G>A (p.Arg719Gln)

ClinVar: 14107 https://www.ncbi.nlm.nih.gov/clinvar/variation/14107/

gnomAD: Not in gnomAD

CaseHCM085: 49 yrs report, Vietnam, Asian

DiseaseAssertion: Hypertrophic Cardiomyopathy

FamilyInfo: N/A

CasePresentingHPOs: HP:0001712, HP:0002875, HP:0011103, HP:0031295, HP:0001653, HP:0001279 (Left ventricular hypertrophy, Exertional dyspnea, Abnormality of the left ventricular outflow tract, Left atrial enlargement, Mitral regurgitation, Syncope)

HPOsFreeText: Maximal LV thickness 19 mm

CaseNotHPOs: HP:0005110, HP:0001297, HP:0004756 (Atrial fibrillation, Stroke, Ventricular tachycardia)

NotHPOsFreeText: N/A

CaseAddInfo: N/A

CasePreviousTesting: The gene panel included 10 sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, MYL2, MYL3, ACTC1, TNNC1, MYH6), 9 genes encoding Z-disk components and Ca2+ homeostasis factors (LDB3, CSRP3, TCAP, VCL, ACTN2, MYOZ2, NEXN, JPH2, PLN), and 4 genes involved in HCM phenocopies (GLA, LAMP2, PRKAG2, TTR), All probands had left ventricular wall thickness >= 15 mm and no other diseases that can cause secondary hypertrophy

CaseGenotypingMethod: The coding region, flanking sequences, and untranslated regions of each gene were enriched by LC-PCR, amplified, and sequenced on the Illumina MiSeq or MiniSeq platform. Identified variants were then filtered for pathogenicity and confirmed by Sanger sequencing.

Variant: NM_000257.4(MYH7):c.1750G>A (p.Gly584Ser)

ClinVar: 42862 https://www.ncbi.nlm.nih.gov/clinvar/variation/42862/

gnomAD: Not in gnomAD

Case1: female, 15 years old at last clinical evaluation

DiseaseAssertion: LVH, HCM

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: cleft mitral valve during intrauterine life

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: evaluated previously by using a DHPLC/Sanger test to search for causative mutations within the exons of 8 sarcomeric genes: MYH7, MYBPBC3, TNNI3, TNNT2, TPM1, ACTC, MYL2, and MYL3

GenotypingMethod: Next generation sequencing, High-Throughput Sequencing

Variant: NM_000257.4:c.976G>C

ClinVar: 43117

CAID: CA017063

gnomAD: https://gnomad.broadinstitute.org/variant/14-23899792-C-G

0.0001627 European (non-Finnish)

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:

Case72: GT76, Male, 54 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002239, HP:0032551

(Gi bleeding, hemorrhoids)

CaseHPOFreeText: Moderate bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Type unknown for this proband

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.2421G>A (p.Trp807Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399796017

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case8: GT9, Male, 86, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Moderate mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 10-20% 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.665T>C (p.Leu222Pro) and NM_000212.2:c.1871G>A (p.Cys624Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224887 and CA400032726

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case42: GT42, Male, 15 years old, Egyptian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0012541, HP:0002239, HP:0031364, HP:0030137

(Cephalohematoma, GI bleeding, ecchymosis, prolonged bleeding after 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: ITGA2B

Variant: NM_000419.3:c.2148dup (p.Leu717Alafs*3)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940304

gnomAD: N/A

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:

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:

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:

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

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:

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:

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:

Case53: GT53, Male, 16 years old, Argentenian/Brazilian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.356G>A (p.Gly201Ser) and NM_000212.2:c.1697G>A (p.Arg119Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622925 and CA400032338

gnomAD: MAF in the African population is http://gnomad.broadinstitute.org/variant/17-45360910-G-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