Supplementary Table S1 & S2 Proband and Variant Information:

Case20: GT23, Male, 19, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Easy bruising, gingival bleeding, 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.1031A>C (p.Tyr344Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025814

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case6: GT7, Female, 19, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: 1 brother, that is all the information Supp table S1 gives us

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 and HP:0000421

(Easy bruising and epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent ADP but some response with other agonists (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.187C>T (p.Arg63Cys) and NM_000212.2:c.505C>T (p.Arg169Ter)

LegacyVariant: N/A

ClinVar: 631774

CAiD: CA8622892 and CA291224658

gnomAD: MAF in the East Asian population is 0.00005012 http://gnomad.broadinstitute.org/variant/17-45360741-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case9: GT10, Male, 45, French and Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mild lifelong bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 30-50% variant expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Residual platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 50232

CAiD: CA913184940 and CA10575572

gnomAD: MAF in the European (non-Finnish) population 0.00006482 http://gnomad.broadinstitute.org/variant/17-45363676-T-C and MAF in the European (non-Finnish) population is 0.000008801 http://gnomad.broadinstitute.org/variant/17-42449775-C-T

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:

Case54: GT54, Male, 33, Argintinian/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0006298

(Gingival bleeding, bleeding following tooth extraction)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.2014+1G>A and a "LR deletion variant" as mentioned in Sup Table 1

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400033055

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case70: GT74, Female, 14 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002239, HP:0002249

(GI bleeding, melena)

CaseHPOFreeText: Serious mouth bleeding, post traumatic heavy bruising, heavy bleeding after adenoid removal

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.1214T>C (p.Ile405Thr) and NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950815 and CA913184940

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case30: GT34, Male, 15 years old, US

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1553T>A (p.Ile518Asn) and NM_000419.3:c.1946+3G>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603038 and CA626121071

gnomAD: MAF in the European (non-Finnish) is 0.000008790 http://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population is 0.000 http://gnomad.broadinstitute.org/variant/17-42456008-C-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case11: GT12, Female, 61, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Brother (died at birth) this is all the information Supp table S1 gives

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978, HP:0000790

(Epistaxis, easy bruising, hematuria)

CaseHPOFreeText: Heavy bleeding and menarche

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case25: GT28, Male, 36, French/Syrian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister (See Supplemental Table 1)

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: "LR Dup" (See Supplementary Table 1)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case59: GT61, Female, 49 years old, French/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000132

(Easy bruising, menorrhagia)

CaseHPOFreeText: Tonsil 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.224del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: MAF in the European (non-Finnish) population is 0.000008795 https://gnomad.broadinstitute.org/variant/17-45360777-TG-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case34: GT36b, Male, 60 years old, Spanish

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406

(Recurrent epistaxis)

CaseHPOFreeText: Embolism of the submaxillary artery

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399806881 and CA913184940

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case66: GT69, Female, 32 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0004406, HP:0000132, HP:0004846

(Bruising, purpura, recurrent epistaxis, menorrhagia, prolonged bleeding after surgery)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0006298 (Prolonged bleeding after dental extraction)

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.1878G>C (p.Gln626His)

LegacyVariant: N/A

ClinVar: 2903

CAiD: CA115852

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case32: GT35b, Female, 16 years old, USA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is 35a in this study (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B and ITGB3

Variant: ITGB3: NM_000212.2:c.392G>C (p.Arg131Pro) and NM_000212.2:c.777+1G>A ITGA2B: NM_000419.3:c.2264G>A (p.Arg755Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

gnomAD: MAF in the African population is 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C, MAF in the Latino population is 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A, MAF in the Latino population is 0.0001903 http://gnomad.broadinstitute.org/variant/17-42454380-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case5: GT6, Female, 19, French/Algerian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 and HP:0000225

(Easy bruising, gingival bleeding)

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asl314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case16: GT19, Female, 44, French (Gypsy)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Brother and cousin are other affected family members (This is all the information we are given, see Supplementary Table 1)

ParentalGenotype: N/A

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

(Easy bruising, menorrhagia, epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A (p.Val513Leufs*71)

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case24: GT27, Female, 84 at death, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0002239

(Ecchymosis, GI bleeding)

CaseHPOFreeText: Bleeding following 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: ITGA2B

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

LegacyVariant: N/A

ClinVar:

CAiD: CA290950376 and CA399795351

gnomAD: MAF in the European (non-Finnish) population 0.000008791 http://gnomad.broadinstitute.org/variant/17-42457994-G-C MAF in African population is 0.000 http://gnomad.broadinstitute.org/variant/17-42453334-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case61: GT64, Female, 26 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Epistaxis, easy bruising, menorrhagia, gingival bleeding, ecchymosis)

CaseHPOFreeText: Mouth and tonsil 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.257T>C (p.Leu86Pro) and NM_000419.3:c.1440-13_1440-1del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290956162 and CA913184940

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case29: GT33b, Female, age not specified, USA/Laos

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 33a in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: Life-threatening bleeding at onset of menses

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8623443

gnomAD: MAF in the Other population is 0.0001385 http://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case3: GT4, Male, 6, French (Gypsy)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967, HP:0001945 HP:0002719

(Petechiae, fever, infections, recurrent infections)

CaseHPOFreeText: Severe bleeding, hematomas since childbirth

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 50% expression of αIIbβ3 and no binding of PAC-1 after activation (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1544+1G>A (p.Val513Leufs*71)

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case18: GT21, Female, 61, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.2864T>A (p.Leu955Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA399791171

gnomAD: N/A

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:

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:

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

Case1: (Proband CabGT-1) Male, age not specified, China

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Surface expression detected by flow cytometry showed <5% GPIIb and <5% GPIIIa

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.531T>A (p.Cys177Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290955739

gnomAD N/A

Case7: (Proband CabGT-7) 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 11% 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: The first variant was found to be: NM_000419.3:c.1563T>A (p.Cys521Ter) and they did not find the second mutation

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950094

gnomAD N/A

Case17: (Proband CabGT-17), 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 13% GPIIb and 27% 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.2929C>T (p.Arg977Ter) and the other mutation could not be found

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602528

gnomAD MAF in the South Asian population is 0.00003266 https://gnomad.broadinstitute.org/variant/17-42452041-G-A

Case24: (Proband Cab-GT24), Female, 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% GPIIb and 10% GPIIIa

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.740G>A (p.Gly247Asp) and NM_000212.2:c.836A>T (p.Lys279Met)

LegacyVariant: N/A

ClinVar: 13569 and 13568

CAiD: CA123256 and CA123254

gnomAD MAF in the African population is 0.00006152 https://gnomad.broadinstitute.org/variant/17-45364494-A-T

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

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

Case2: Male, 10 years old, Andra Pradesh India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Epistaxis, ecchymosis, GI bleeding, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.475G>A (p.Gly159Ser)

LegacyVariant: (p.Gly128Ser)

ClinVar: N/A

CAiD: CA8603454

gnomAD: MAF in the South Asian population is 0.00003267 https://gnomad.broadinstitute.org/variant/17-42463018-C-T

Case1: Male, 13 years old, Andra Pradesh India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0006298, HP:0000421, HP:0000967, HP:0002239, HP:0000225

(Prolonged bleeding after dental extraction, epistaxis, petechiae, GI bleeding, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.48G>A (p.Trp16Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399807046

gnomAD: N/A

Case5: Female, 28 years old, Goa India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0002239, HP:0000225, HP:0006298, HP:0000967, HP:0000132

(Ecchymosis, GI bleeding, gingival bleeding, prolonged bleeding after tooth extraction, petechiae, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: IVS15-1 G>A can't be found in the allele registry by me I am noting it as Unreg

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603039

gnomAD: N/A

Case3: Male, 6 years old, Andra Pradesh India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000225

(Ecchymosis, gingival bleeding)

CaseHPOFreeText: Bleeding during tooth extraction

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.952T>A (p.Ser318Leu)

LegacyVariant: (p.Ser287Leu)

ClinVar: N/A

CAiD: CA399804792

gnomAD: N/A

Case1: Male, French, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A "Has no surviving close relatives"

ParentalGenotype:

CasePresentingHPOs: HP:0002239 (GI bleeding)

CaseHPOFreeText: Hemorrhage

CaseNotHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseNotHPOsFreeText: N/A

ProteinExpression:

PlateletAggregation: Total lack of platelet aggregation in response to physiologic agonists and also defective clot retraction

CasePreviousTesting: Direct sequencing of all exons and splice sites of ITGA2B was performed and sequencing of the 15 exons, splice sites, and promoter of ITGB3 was also performed

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 European (non-Finnish) population 0.000008791 http://gnomad.broadinstitute.org/variant/17-42457994-G-C and MAF in the Latino population is 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Tables 1 and 2 combined information:

Case20a: GT20a, Male, 30 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Family information available in Table1 (brother of GT20b)

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000225

(Gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

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

Supplementary Tables 1 and 2 combined information:

Case42: GT42, Female, 9 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

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

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1300del (p.Gln434fs) Note in google doc to ask

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940256

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case16: GT16, Male, 31 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro)

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case32: GT32, Male, 9 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

CasePresentingHPOs:HP:0000421

(Epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.886G>A (p.Gly296Arg) and NM_000419.3:c.460_462del (p.Glu154del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603306 (p.Gly296Arg) and CA8603457 (p.Glu154del)

gnomAD: MAF in East Asian population: 0.00005454 https://gnomad.broadinstitute.org/variant/17-42461684-C-T and MAF in European (non-Finnish) population 0.000008870 https://gnomad.broadinstitute.org/variant/17-42463030-TCTC-T

Supplementary Tables 1 and 2 combined information:

Case9: GT9, Female, 25 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421, HP:0000132

(Epistaxis, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case15b: Male, 9 years old, brother to GT15a

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1, brother to GT15a

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Platelet aggregation showed a small response to ADP and collagen but normal response to ristocetin

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case17b: GT17b, Male, 15 years old, brother of GT17a

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per supplementary table 1

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

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0002239

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

CaseHPOFreeText: Post traumatic hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602626 (p.Gln891Ter)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case24: GT24, Female, 7 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.1750C>T (p.Arg584Ter) This article is still being done-Meera)

LegacyVariant: N/A

ClinVar: 225393 (p.Gln778Pro) and 2892 (p.Arg584Ter)

CAiD: CA290947544 (p.Gln778Pro) and CA115834 (p.Arg584Ter)

gnomAD: MAF in East Asian population: 0.0002176 (p.Arg584Ter) https://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF in East Asian population for p.Gln778Pro 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Tables 1 and 2 combined information:

Case11: GT11, Female, 12 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case18: Gt18, Male, 20 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2671C>T (p.Gln891Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602626 (p.Gln891Ter)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case36: GT36, Male, 8 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0002239

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

CaseHPOFreeText: Intestinal intrussusception

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623377

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

Supplementary Tables 1 and 2 combined information:

Case27: GT27, Male, 29 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

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

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

(Bruising, purpura, ecchymosis)

CaseHPOFreeText: Post traumatic hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) This article is not completed-Meera

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

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

Supplementary Tables 1 and 2 combined information:

Case10: GT10, Male, 8 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399798321

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case15a: Male, 15 years old, brother to GT15b

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1, brother to GT15b

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case1: GT1, Female, 5 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

(Bruising, purpura, ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1051C>T (p.Arg351Ter) and NM_000419.3:c.2029G>A (p.Glu677Lys)

LegacyVariant: N/A

ClinVar: N/A

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

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case39: GT39, Male, 25 years old

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: HP:0100309 (Subdural hematoma)

CaseHPOFreeText: Post traumatic hemorrhage

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Showed 50-100% (variant) of αIIbβ3 expression measured by flow cytometry

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2570G>T (p.Cys857Phe) and NM_000419.3:c.1769G>A (p.Arg590Gln)

LegacyVariant: N/A

ClinVar: N/A

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

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

Supplemental Table S1:

Cases6-11: Males and Females from India/Pakistan, ages not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate to severe bleeding tendency in these patients

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

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

PreviouslyPublished: PMID: 19172520 and 26896847

Supplemental Table S1:

Cases 13-18: Males and Females, from Sweden, France and Germany and other places, ages are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate to severe bleeding when data was available

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 5%/<5% when homozygous αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2900

CAiD: CA115846

gnomAD: MAF in the European non finnish pop is 0.0001325 https://gnomad.broadinstitute.org/variant/17-42457148-A-G

PreviouslyPublished: PMID: 9215749, 9734640, 20020534, 22513797, 25373348

Supplemental Table S1:

Cases19-23: Males and Females from France, North Africa, Italy and Germany, ages are not specified for these patients

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1878G>T (p.Gln626His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801470

gnomAD: N/A

PreviouslyPublished: PMID: 21113249, 20020534, 22513797, 25728920

Supplemental Table S1:

Case24: N/A (from Turkey)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Individual clinical data not given

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: Thr646Ala* (Need to consult senior biocurator to figure this variant out) will note it as Unknown as I am not sure of it

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

PreviouslyPublished: PMID: 25734216

Supplemental Table S1:

Cases35and36: Females, USA, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2264G>A (p.Arg755Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602771

gnomAD: MAF in the Latino population is 0.0001903 https://gnomad.broadinstitute.org/variant/17-42454380-C-T

PreviouslyPublished: PMID: 25728920

Supplemental Table S1:

Case1: Male, China, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406, HP:0000225, HP:0000979

(Recurrent epistaxis, gingival bleeding, and purpura)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 14% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1429G>C (p.Ala477Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399803370

gnomAD: N/A

PreviouslyPublished: PMID: 15946231

Supplemental Table S1:

Case34: Female, Germany, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate to severe bleeding that prompted transfusion

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: (p.Cys705Leu) not getting this to show up in CAR need to consult senior biocurator noting this as Unknown Variant --> Variant can't be identified

LegacyVariant: N/A

ClinVar: N/A

CAiD: ^

gnomAD: ^

PreviouslyPublished: PMID: 20345392

Supplemental Table S1:

Case25: Female, Italy, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2051T>G (p.Leu684Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399799849

gnomAD: N/A

PreviouslyPublished: PMID: 21113249

Supplemental Table S1:

Case37: Female, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mild bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602772

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

PreviouslyPublished: PMID: 19172520

Case1: Female, 35 years old, Italian

DiseaseAssertion: Macrothromocytopenia

FamilyInfo: See Supp. Fig S1 for pedigree

ParentalGenotype: See Supp. Fig S1 for pedigree

CasePresentingHPOs: N/A

CaseHPOFreeText: Life-long moderate to severe bleeding, mainly mucocutaneous

CaseNotHPOs: N/A

CaseNotHPOsFreeText: No abnormalities in blood clotting

ProteinExpression: Flow cytometry showed mild reduction of surface αIb β3

PlateletAggregation: Impaired platelet aggregation to physiological agonists but not to ristocetin,

CasePreviousTesting: ITGA2B and ITGB3 were amplified and sequenced

Gene: ITBG3

Variant: NM_000212.2:c.2134+1G>C

LegacyVariant: N/A

ClinVar: 50228

CAiD: CA143711

gnomAD: N/A

Case#: 40 yo, Female, W. Turkey

DiseaseAssertion: Glanzmann Thrombasthenia

FamilyInfo: Consanguineous (cousins).

ParentalGenotype: Both carriers.

CasePresentingHPOs: (HP:0007420) Spontaneous hematomas, (HP:0001892) Abnormal bleeding, (HP:0100608) Metrorrhagia, (HP:0001935) Microcytic anemia, (HP:0034263) Abnormal vaginal bleeding, (HP:0004944) Cerebral aneurysm,

PlateletAggregation: Hypochromic anemia and a platelet count of 198 × 109/L (normal range 150–400 × 109/L). Platelet aggregometry showed no aggregation after stimulation with collagen (2 and 10 µg/mL), ADP (4 and 10 µmol/L), and epinephrine (8 µmol/L) (norm > 70%), and reduced (42%, Norm > 70%) agglutination after stimulation with ristocetin (1.2 mg/mL).

CaseHPOFreeText: Received platelet concentrates multiple times as a young adult before dental surgery. Pregnancy, alloantibodies to glycoprotein αIIbβ3 were detected in the patient’s blood. emergency caesarean section was performed in another hospital. Because the patient developed severe bleeding problems, she received two red cell units, two pooled platelet concentrates, tranexamic acid, and desmopressin intraoperatively. Two drainages were placed. Three platelet concentrates were transfused in the following days, resulting in a first-time transfusion reaction. Emergency cesarean- endometrial coagulation, operative hysteroscopy.

ProteinExpression: Flow cytometry showed the absence of expression of CD41 (integrin αIIbβ3) and severely impaired fibrinogen binding after ADP activation

CasePreviousTesting: molecular genetic analysis was performed using a custom gene panel for inherited platelet disorders (Nextera Rapid Custom Enrichment, Illumina, San Diego, CA, USA) established in our department, followed by sequencing on a MiSeq (Illumina)

Gene: ITGA2B

HGVS: 6138

ClinVar: Unregistered

CAID: CA2261369696

gnomAD: Absent

Gene: ITGA2B

HGVS: 6138

ClinVar: Unregistered

CAID: CA2261369696

gnomAD: Absent

Case1: Male, 3.5 years old, Indian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: (HP:0000421 Epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1286G>A (p.Asp396Asn)

LegacyVariant: (p.Asp365Asn)

ClinVar: N/A

CAiD: CA399803675

gnomAD: N/A

Case11: Female, 5 years old, Indian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sibling is proband number 12 in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000421 (Ecchymosis, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802454

gnomAD: N/A

Case51: (GT-63) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

Variant: NM_000419.3:c.558C>G (p.Tyr186Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805728

gnomAD: N/A

Case40: (GT-50) Male, 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

Case9: (GT-11) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT12 -GT14 are related to GT-11 see Table 1

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

Case38: (GT-48) Male, 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

Case16: (GT-18) Female, carrier status, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-18 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 on bleeding phenotype/severity (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

Case55: (GT-74) Male, 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.437T>C (p.Leu146Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400021960

gnomAD: N/A

Case29: (GT-34) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

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

Case1: (GT-01) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: Probands 2-9 are related to GT-01 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 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

Case32: (GT-37) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Case20: (GT-22) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: 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.2302-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034626

gnomAD: N/A

Case49: (GT-60) 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

Case22: (GT-26) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT-26 is related to GT-25 see Table 1

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: 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: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry performed and CD41 and CD61 not observed (See Supplementary Table 3)

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

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

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

Case12: Patient TA, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: His son is Patient TE

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

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

Gene: ITGA2B and ITGB3

Variant: ITGA2B variant: NM_000419.3:c.3060G>A and ITGB3 variant: NM_000212.2:c.856G>A (p.Gly286Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500261104 and CA400020688

gnomAD: MAF in the European (non-Finnish) population is 0.00001760 https://gnomad.broadinstitute.org/variant/17-45364514-G-A for the ITGB3 variant

Case1: Patient OK, gender, age, ethnicity not specified