Supplementary Table S1 & S2 Proband and Variant Information:

Case10: GT11, Female, 54, French and German

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Epistaxis, gingival bleeding, menorrhagia)

CaseHPOFreeText: Spontaneous bruising

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: N/A

ClinVar: 2896 and 381748

CAiD: CA115839 and CA8603182

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case23: GT26, Male, 45, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978

(Epistaxis, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

Case1: Female, 14 years old, German

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: Severe hemorrhage after tonsillectomy, bleeding after shedding off her deciduous teeth, prolonged cutaneous bleeding time > 20 minutes

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Flow cytometry revealed that the proband expressed only 7-10% of GPIIb-IIIa on the platelet surface

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

CasePreviousTesting: Sequence analysis of PCR amplifeid platelet GPIIb mRNA was performed

Gene: ITGA2B

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

LegacyVariant: (p.Arg327His)

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

Supplementary Table S1:

Case10: GT11, French/German, 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.1073G>A (p.Arg385His) NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: N/A

ClinVar: 2896 and 381748

CAiD: CA115839 and CA8603182

gnomAD: MAF in the Latino population for (p.Gly412Arg) is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

Case6: Female, age not specified, Germany

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: N/A

Platelet Aggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)

Note: This article mentions this patient as having a G391R mutation; however, this article cites this patient in citation 6; where that article states this patient has a G412R mutation. There is some typo here. I am using the information given in Reference 6. The proband is #11 in reference 6.

LegacyVariant: (p.Arg327His) (Not writing legacy for the other variant, as there is some typo between articles)

ClinVar: 2896 for the (p.Arg358His) mutation and 381748 for (p.Gly412Arg)

CAiD: CA115839 for (p.Arg358His) and CA8603182 for (p.Gly412Arg)

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

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

Case8: Patient Mila-1 (found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 25% 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 number 19 in this article

Case1: Female, 22 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1

ParentalGenotype: The patient's parents revealed reduced concentrations of glycoprotein llb-Illa and were considered to be heterozygotes. See Fig 1

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

(Severe epistaxis, gingival bleeding, menorrhagia, spontaneous bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Platelets had much reduced alphaIIb3 when estimated by crossed immunoelectrophoresis

PlateletAggregation: Platelet aggregation was absent with ADP, arachidonic acid, and collagen.

CasePreviousTesting: Sequenced all exons and splice sites of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: (p.Arg327His) and (p.Gly381Arg)

ClinVar: 2896 and 381748

CAiD: CA115839 and CA8603182

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

PreviouslyPublished: PMID: 3762006 proband is mentioned in this article

Case10: (GT45) 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: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD N/A