Case1: Female, Indian, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Parents are heterozygous for the mutation of interest

CasePresentingHPOs: HP:0000978 (Easy bruising)

CaseHPOFreeText: Subsequent episodes of excessive bruising

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: N/A

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

CasePreviousTesting: Haplotype analysis was performed using polymorphic markers on chromosome 17q12–21, which included dinucleotide repeat polymorphisms (CA)n in BRCA1 gene and locus D17S579 and (CT)n within GP IIIa intron6, and the known restriction fragment length polymorphism(RFLP) markers, Fok I (GP IIb exon 26), Taq I (GP IIIa exon 8) andSma I (GP IIIa exon 9)

Gene: ITGB3

Variant: IVS1-14C>A (Unregistered Variant)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Supplementary Table S1:

Case38: GT44, 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: ITGA2B

Variant: NM_000419.3:c.1357C>T (p.Arg453Ter)

LegacyVariant: N/A

ClinVar: 631773

CAiD: CA399803529

gnomAD: N/A

Supplementary Table S1:

Case54: GT64, French, age and gender 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.257T>C (p.Leu86Pro) and NM_000419.3:c.1440-13_1440-1del (p.Arg480SerfsTer106)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290956162 and CA913184940

gnomAD: N/A

Supplementary Table S1:

Case7: GT8, 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.2348+5G>C

LegacyVariant:

ClinVar: N/A

CAiD: CA290947484

gnomAD: N/A

Supplementary Table S1:

Case50: GT58, Argentinian/European, 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.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1:

Case61: GT72, French, age 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: ITGA2B

Variant: NM_000419.3:c.2951C>A (p.Thr984Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399790180

gnomAD: N/A

Supplementary Table S1:

Case16: GT19, French Gypsy, 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: ITGA2B

Variant: NM_000419.3:c.1544+1G>A (p.Val513Leufs*106)

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Supplementary Table S1:

Case4: GT5, French, 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: ITGB3

Variant: NM_000212.2:c.565C>T (p.Pro189Ser) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669 and CA8623443

gnomAD: MAF in the European (non-Finnish) population is 0.00002638 https://gnomad.broadinstitute.org/variant/17-45362012-C-T and MAF in the East Asian population is 0.0001087 https://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1:

Case20: GT23, 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: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025814

gnomAD: N/A

Supplementary Table S1:

Case22: GT25, 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.1413C>G (p.Tyr471Ter) and NM_000419.3:c.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950376 and CA399801310

gnomAD: MAF in the European (non-Finnish) population is 0.000008791 for (p.Tyr471Ter) and MAF in the Latino population is 0.00003983 for the (p.Arg628Ter) variant https://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Table S1:

Case12: GT13, 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: 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 https://gnomad.broadinstitute.org/variant/17-42457372-G-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

Case: Female, Ashkenazi Jewish, 2 days old at presentation

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: consanguineous marriage, pedigree in Figure 4

ParentalGenotype: Mother carrier of Gly273Asp. Father carrier of Gly273Asp.

CasePresentingHPOs: HP:0100309, HP:0000978, HP:0003010, HP:0004866, HP:0008320, HP:0008148, HP:0000421, HP:0001975

(subdural bleeding, extensive ecchymoses, prolonged cutaneous bleeding time, absent platelet aggregation in response to ADP, absent platelet aggregation in response to collagen, absent platelet aggregation in response to epinephrine, occasional epistaxis, markedly decreased number of GPIIb-IIIa heterodimers)

CaseHPOFreeText: NA

CaseNotHPOs: HP:0011873, HP:0011871

(normal platelet count, normal platelet agglutination in response to ristocetin)

CaseNotHPOFreeText: NA

ProteinExpression: <5% of the normal amount of GPIIb-GPIIIa; measured by flow cytometry

CasePreviousTesting: PCR amplification of genomic DNA and DNA sequence analysis of the GPIIb coding sequence only.

Gene: ITGA2B

Variant: NM_000419.3:c.818G>A p.(Gly273Asp)

LegacyVariant: NA

ClinVar: 2894

CAID: CA115837

gnomAD: NA

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-17 see Table 1

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case31: (GT-36) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

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

Case37: (GT-47) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT45-GT48 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: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Case7: (GT-08) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-08 see Table 1

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry results not available (See Supplemental Table 3)

PlateletAggregation: No 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

Case39: (GT-49) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT49-GT52 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

Case4: (Proband CabGT-4), Female, age not specified, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed surface expression as 53% GPIIb and 66% GPIIIa

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGA2B

Variant: c.1442-13_1442-1del (This variant does not show up in the CAR or ClinVar)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD N/A

Case18: (Proband CabGT-18), Gender, age and ethnicity were not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: N/A

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 381747 (p.Val982Met) and 417951 (p.Ala989Thr)

CAiD: CA16608466 (p.Val982Met) and CA8602498 (p.Ala989Thr)

gnomAD MAF in the European (non-Finnish) population is 0.00006486 https://gnomad.broadinstitute.org/variant/17-42451838-C-T and MAF in the Other popeulation for (p.Ala989Thr) is 0.001939 https://gnomad.broadinstitute.org/variant/17-42451817-C-T

Case13: (Proband CabGT-13) Male, age not specified, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% of GPIIIa and GPIIb surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

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

Case20: (Proband CabGT-21), Male, age not specified, North African

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% GPIIIa and GPIIb surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGB3

Variant: NM_000212.2:c.100C>T (p.Arg34Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622852

gnomAD MAF in the African population is 0.00008013 https://gnomad.broadinstitute.org/variant/17-45351805-C-T

Case11: (Proband CabGT-11) Female, age not specified, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% GPIIb and 20% GPIIIa surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGA2B

Variant: NM_000419.3:c.1787T>C (p.Ile596Thr)

LegacyVariant: N/A

ClinVar: 2900

CAiD: CA115846

gnomAD MAF in the European (non-Finnish) population is 0.0001325 https://gnomad.broadinstitute.org/variant/17-42457148-A-G

Case5: (Proband CabGT-5), Female, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% of both GPIIIa and GPIIb

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGA2B

Variant: c.1442-13_1442-1del, and Table 1 notes that the second mutation was not found

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD N/A

Case23: (Proband CabGT-23) Female, age not specified, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed 10% GPIIb and 14% GPIIIa surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGB3

Variant: NM_000212.2:c.665T>C (p.Leu222Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224887

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

Case12: GT41, Male, India, age of onset is 3 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGA2B

Variant: NM_000419.3:c.727del (p.Leu243PhefsTer62)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940727

gnomAD: N/A

Case8: GT27, Male, India, age of onset is 3 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGA2B

Variant: NM_000419.3:c.800-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805152

gnomAD: N/A

Case27: GT34, Female, India, age of onset is 5 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGB3

Variant: NM_000212.2:c.1402G>T (p.Glu468Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400029121

gnomAD: N/A

Case4: GT14, Female, India, age of onset is 3 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGA2B

Variant: c.575-22A>C the CAR is not pulling this variant up --> I will note this as Unregistered; however a senior biocurator may be able to parse this out

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

Case37: GT64, Female, India, age of onset is 16 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Case31: GT48, Male, India, age of onset is 5 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation

CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case63: GT66, Female, 15 years old, French/Ko

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected cousin (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000175, HP:0000225, HP:0000421, HP:0031364

(Cleft palate, gingival bleeding, epistaxis, ecchymosis)

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: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

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

CaseHPOFreeText: Hematomas, oropharynx bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940309

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

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

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Severe epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023344 and CA8623025

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case39: GT40, Female, 17 years old, Pankistani

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0030140

(Epistaxis, bleeding from mouth)

CaseHPOFreeText: Heavy bleeding at menarche

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.857T>A (p.Val286Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805011

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case50: GT50, Male, 78 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000225

(Ecchymosis, gingival bleeding)

CaseHPOFreeText: Moderate bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623200

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case4: GT5, Male, 7, French

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

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

(Epistaxis, easy bruising, subararachnoid hemorrhoid)

CaseHPOFreeText: Post-traumatic bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.565C>T (p.Pro189Ser) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669 and CA8623443

gnomAD: MAF in the European (non-Finnish) population is 0.00002638 http://gnomad.broadinstitute.org/variant/17-45362012-C-T and MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case71: GT75, Female, 9 years old, French/African

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Ecchymosis, epistaxis, gingival bleeding)

CaseHPOFreeText: Lots of deciduous teeth with bleeding, hematomas in the eye and under the clavicle

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed less than 5% 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.*165T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940530

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case2: GT3, Female, 32, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000979, HP:0002239

(Epistaxis, ecchymosis, purpura, GI bleeding,)

CaseHPOFreeText: Excessive menstrual bleeding, proband sometimes hospitalized with severe symptoms

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.353T>A, NM_000212.2:c.709_710del, NM_000212.2:c.1732G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224511, CA8623029 and CA8623343

gnomAD: MAF in the European non Finnish populationis 0.00001796 http://gnomad.broadinstitute.org/variant/17-45363717-CAG-C and MAF in the Other popualation is 0.0008149 http://gnomad.broadinstitute.org/variant/17-45376715-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case57: GT58, Male, 14, Argentinian/European

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000967, HP:0000225, HP:0011886

(Epistaxis, petechia, gingival bleeding, hyphema)

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.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case49: GT49, Female, 16 years old, French/Spanish

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000421

(Ecchymosis, epistaxis)

CaseHPOFreeText: Post-traumatic hematomas, proband has severe epistaxis

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.2113T>C (p.Clys705Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA8602816

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case36: GT38, Female, 9 years old, Swiss

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0002239

(Petechiae, easy bruising, 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: 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 & 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

Case7: Female, elderly (age not specified)

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding when younger

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

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

Case14: Female, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate bleeding tendency

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting: None

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: MAF in European non Finnish population 0.000008795 http://gnomad.broadinstitute.org/variant/17-45360777-TG-T

Case35: Patient Chinese 20 (found in GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Epistaxis, menorrhagia, purpura/petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <15% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562

CAiD: CA123244

gnomAD: N/A

PreviouslyPublished: References 57 and 58

Case40: Patient P

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 44% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13556

CAiD: CA123230

gnomAD: N/A

PreviouslyPublished: References 63-65

Case7: Patient KJ (can be found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0006298 (Bruising, prolonged bleeding after dental extraction)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 7-10% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

PreviouslyPublished: Reference 18 in this article

Case16: Family II (patient found in the GT database as well) gender and age are not specified here

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

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

PreviouslyPublished: Reference number 28 in this article

Case21: Patient MC gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Gingival bleeding HP:0000225

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <12% of normal

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: M_000419.3:c.3060+2T>C and NM_000419.3:c.3094dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290944108 and CA915940756

gnomAD: MAF in the European (non-Finnish) population is 0.00003876 https://gnomad.broadinstitute.org/variant/17-42451720-A-G

PreviouslyPublished: References 34-36

Case18: Iranian-Jewish patient (found in the GT database), gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucous membrane bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Minimal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.113del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940264

gnomAD: N/A

PreviouslyPublished: Reference number 30

Case29: Strasbourg 1

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Bruising HP:0000978

CaseHPOFreeText: Hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.718C>T (p.Arg240Trp)

LegacyVariant: N/A

ClinVar: 13555

CAiD: CA123228

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

PreviouslyPublished: Ref 46, 47

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A Not reported for this proband

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Undetectable for this patient

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399803552

gnomAD: N/A

PreviouslyPublished: Reference number 20 in this article

Case22: Patient AP, gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

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

CaseHPOFreeText: Hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 12-20% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 50232

CAiD: CA10575572

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

PreviouslyPublished: References 37 and 38

Case11: Patient Gypsy (found in the GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Blood transfusions required

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Decreased surface expression of GPIIIa and GPIIb

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

PreviouslyPublished: Reference number 22 in this article

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression to be <5%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGA2B

Variant: NM_000419.3:c.693dup (c.692insT)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940315

gnomAD: N/A

PreviouslyPublished: PMID: 12083483

Case8: GT-8, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression to be < 5%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGA2B

Variant: NM_000419.3:c.2965del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913189248

gnomAD: N/A

Case7: GT-7, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression to be between 5% and 20%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGB3

Variant: NM_000212.2:c.431T>G (p.Met144Arg)

LegacyVariant: (p.Met118Arg)

ClinVar: N/A

CAiD: CA291224645

gnomAD: N/A

Case6: GT-6, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression to be <5%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

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.1612G>T (p.Glu538Ter)

LegacyVariant: (p.Val951Met) and (p.Ala958Thr) and (p.Glu507Ter)

ClinVar: 381747 and 417951

CAiD: CA16608466 (p.Val951Met) and CA8602498 (p.Ala958Thr) and CA399802424 (p.Glu538Ter)

gnomAD: MAF in European (non-Finnish population) 0.00006486 http://gnomad.broadinstitute.org/variant/17-42451838-C-T and MAF in other population is 0.001939 http://gnomad.broadinstitute.org/variant/17-42451817-C-T

PreviouslyPublished: PMID: 15099289(p.Val951Met) and (p.Ala958Thr)

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression to be <5%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGB3

Variant: M_000212.2:c.647A>G (p.Tyr216Cys)

LegacyVariant: (p.Tyr190Cys)

ClinVar: N/A

CAiD: CA400023432

gnomAD: N/A

Case3: GT-3, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed αIIbβ3 expression between 5% and 20%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGA2B

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

LegacyVariant: (p.Cys674Arg) +31=705

ClinVar: N/A

CAiD: CA8602816

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

PreviouslyPublished PMID: 9920835

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% αIIbβ3 expression

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGA2B

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

LegacyVariant: (p.Leu183Pro) + 31= 214

ClinVar: 2901

CAiD: CA115848 and CA915940289

gnomAD: N/A

PreviouslyPublished PMID: 9473221 (p.Leu214Pro)

Case1: GT-1, gender, age, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: N/A

ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents

CasePresentingHPOs: N/A

CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry revealed αIIbβ3 expression between 5% and 20%

PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.

CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples

Gene: ITGB3

Variant: NM_000212.2:c.448A>G (p.Met150Val) and NM_000212.2:c.774_775del (p.Cys258Ter)

LegacyVariant: (p.Met124Val)

ClinVar: N/A

CAiD: CA8622961 and CA915940285

gnomAD: MAF in South Asian population is 0.00003266 http://gnomad.broadinstitute.org/variant/17-45361895-A-G

PreviouslyPublished PMID: 15583747 (p.Met124Val)

Case32: (GT59) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has one normal borther and one brother who is heterozygous for the mutation

ParentalGenotype: Both parents are heterozygous for this mutation that the proband harbors

CasePresentingHPOs: N/A

CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)

CaseNotHPOs: N/A

ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting

Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)

CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.

Gene: ITGB3

Variant: NM_000212.2:c.155_156delinsTT

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940691

gnomAD N/A

Case18: (GT3) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has one brother and sister without the mutation and has one brother that is heterozygous for the variant

ParentalGenotype: Mother and father are both heterozygous for the mutation

CasePresentingHPOs: N/A

CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)

CaseNotHPOs: N/A

ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting

Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)

CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.

Gene: ITGB3

Variant: NM_000212.2:c.2315T>C (p.Leu772Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034691

gnomAD MAF in the African population is 0.00006152 https://gnomad.broadinstitute.org/variant/17-45387518-T-C

Case14: (GT2), Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: His sister is heterozygous for this mutation

ParentalGenotype: Father and mother are both heterozygous for this mutation

CasePresentingHPOs: N/A

CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)

CaseNotHPOs: N/A

ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting

Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)

CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.

Gene: ITGB3

Variant: NM_000212.2:c.725G>A (p.Arg242Gln) There is a typo in the paper-- it says that the c. is c.752G>A however it is 725

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224896

gnomAD N/A

Case21: (GT62) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)

CaseNotHPOs: N/A

ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting

Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)

CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.

Gene: ITGA2B

Variant: NM_000419.3:c.1559del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940684

gnomAD N/A

Case15: (GT24) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)

CaseNotHPOs: N/A

ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting

Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)

CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.

Gene: ITGB3

Variant: NM_000212.2:c.953T>C (p.Leu318Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025639

gnomAD MAF in the European Finnish population is 0.00004620 https://gnomad.broadinstitute.org/variant/17-45367060-T-C

Case11: Patient LF, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGA2B

Variant: NM_000419.3:c.1912dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940678

gnomAD: N/A

Case22: Patient DOM, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGA2B

Variant: NM_000212.2:c.1801T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623361

gnomAD: MAF in the European non Finnish population is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C

Case7: Patient CT, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGA2B

Variant: NM_000419.3:c.1096C>T (p.Arg366Ter)

LegacyVariant: (p.Arg335Ter)

ClinVar: N/A

CAiD: CA399804480

gnomAD: N/A

Case1: Patient FN, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGA2B

Variant: IVS3(-3)418del (Ala106_Gln111del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: Unregistered

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGA2B and ITGB3

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

LegacyVariant: (p.Pro145Ala)

ClinVar: N/A

CAiD: CA399805793 and CA8622899

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