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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT30 is related to GT29

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

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

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

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

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

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

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034626

gnomAD: N/A

Case#: 5 year old, female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, HP:0004406, HP:0006298, HP:0001892

PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.

GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing

Allele 1:

ClinVar: 953019

CAID: CA8602528

Variant: NM_000419.5:c.2929C>T **wrong AA change reported in paper

GnomAD: South Asia at rate of 0.00003266 (1/30616)

ExpressionEvidence: Flow Cytometry of platelet integrin: .23% B3 expression, .21% A2B expression

Case#: 6 year old, male

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, HP:0000225, HP:0006298, HP:0001892, HP:0002239

PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.

GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing

ClinVar: 2892

CAID: CA115834

Variant: NM_000419.5:c.1750C>T

GnomAD: East Asian Population 0.0002176 (4/18386)

ExpressionEvidence: Flow Cytometry of platelet integrin: .24% B3 expression, .18% A2B expression

Case#: 33 year old, female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0006298

PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.

GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing

ClinVar:

CAID: CA8603182

Variant: NM_000419.5:c.1234G>A

GnomAD: Latino 0.0001453 (5/34414)

ExpressionEvidence:Flow Cytometry of platelet integrin: 1.3% B3 expression, .3% A2B expression

Case#: 1 year old, Female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, HP:0002239

PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.

GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing

ClinVar: 1330328

CAID: CA399801004

Variant: NM_000419.5:c.1993C>T

GnomAD:Found in East Asian population at rate of 0.00005461 (1/18310)

ExpressionEvidence: Flow Cytometry of platelet integrin: 2.8% B3 expression, 36.5% A2B expression

Case2: Patient HLo

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case15: Patient MMc

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

Variant: NM_000419.3:c.2842-1G>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399791378

gnomAD: N/A

Case10: Patient FC

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

Variant: NM_000419.3:c.2540T>C (p.Leu847Pro)

LegacyVariant: (p.Leu816Pro)

ClinVar: N/A

CAiD: CA399794666

gnomAD: MAF in the African population is 0.00006443 https://gnomad.broadinstitute.org/variant/17-42453262-A-G

Case12: Patient Ssab

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGB3

Variant: NM_000212.2:c.1955A>T (p.His652Leu)

LegacyVariant: (p.His626Leu)

ClinVar: N/A

CAiD: CA400032927

gnomAD: N/A

Case16: Patient TG

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

Variant: NM_000419.3:c.3061-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399787972

gnomAD: N/A

Case1: Patient HMJ

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case6: Patient DN

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case12: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0031364, HP:0002249

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

CaseHPOFreeText: Retroperitoneal, haematuria

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case18: Female, Arab, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364

(Epistaxis, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case8: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364, HP:0030137, HP:0002573

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

CaseHPOFreeText: Haemarthrosis, retro-peritoneal bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case22: Female, Arab, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

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

(Epistaxis, gingival bleeding, ecchymosis, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case11: Female, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0031364, HP:0002249

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

CaseHPOFreeText: Colon angiodysplasia, retroperitoneal, haematuria, haemarthrosis

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case1: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

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

(Epistaxis, gingival bleeding, ecchymosis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case4: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002105, HP:0031364

(Epistaxis, hemoptysis, ecchymosis)

CaseHPOFreeText: Intracranial at birth, haematemesis, haematuria

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation:

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.2473_2478delinsTCACCAGGGCCTTCACCTCAGCATCCACC

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940595

gnomAD: N/A

PreviouslyPublished: 7529063

Case21: Male, Iraq, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del (p.Asp677Glufs)

LegacyVariant: (p.Asp651Glufs*3)

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

Case17: Female, Arab, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case15: Male, Arab, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2889

CAiD: CA10575471

gnomAD: N/A

Case2: Female, 17 years old, Portugese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Also studied were the patient’s mother (I.2), her father (I.1), and her brother (II.2). See pedigree below in article

ParentalGenotype: Parents were heterozygous for mutation

CasePresentingHPOs: HP:0000967

(Petechia)

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: <5% surface expression of aIIbb3

PlateletAggregation: Platelet aggregation is absent with ADP, collagen, epinephrine and arachidonic acid among agonists tested but the response was normal with ristocetin

CasePreviousTesting: We examined each of the 30 exons of the b3 gene and each of the 15 exons of the aIIb gene for migration changes in PCR-SSCP analysis

Gene: ITGB3

Variant:

LegacyVariant:

ClinVar: N/A

CAiD:

gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45369648-A-AC

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:

Case41: GT41b, Male, 13 years old, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978

(Epistaxis, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.91del (p.Ala31Profs2) and NM_000419.3:c.2915dup (p.Leu973Alafs63)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913203486 and CA8602531

gnomAD: MAF in the East Asian population is 0.0001088 http://gnomad.broadinstitute.org/variant/17-42452054-C-CG

Supplementary Table S1 & S2 Proband and Variant Information:

Case72: GT76, Male, 54 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002239, HP:0032551

(Gi bleeding, hemorrhoids)

CaseHPOFreeText: Moderate bleeding syndrome

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Type unknown for this proband

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399796017

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

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:

Case26: GT30, Female, age not specified, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother (See Supplementary Table 1)

ParentalGenotype: N/A

CasePresentingHPOs:

(Epistaxis, GI bleeding)

CaseHPOFreeText: Diffuse bruising mainly with trauma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.777+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623036

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case55: GT55, Female, 28, Argentinian/Brazilian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has an affected sister (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000421

(Gingival bleeding, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 11-22% expression of αIIbβ3 (See Supplementary Table 1)

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.647C>T (p.Ala216Val)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805506

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case7: GT8, Male, 82 at death, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0002239

(Easy bruising, epistaxis, GI bleeding

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.2348+5G>C (p.Ser756Gly783delInsArg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290947484

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case68: GT72, Female, 56 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000225, HP:0000132, HP:0002239, HP:0006298

(Epistaxis, ecchymosis, gingival bleeding, menorrhagia, GI bleeding, prolonged bleeding after dental extraction)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399790180

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case52: GT52, Male, 24 years old, Argentenian/Brazil

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Hematomas

(Proband's symptoms decreased during adolescence)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case37: GT39a, Female, 23 years old, Swedish/American

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 39b in this study (See Supplemental Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0006298, HP:0000132

(Bruising susceptibility, epistaxis, prolonged bleeding after dental extraction, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case38: GT39b, Male, 18 years old, Swedish/American

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is proband 39a in this study (See Supplemental Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0006

(Bruising susceptibility, epistaxis)

CaseHPOFreeText: Hematomas after minor trauma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case21: GT24, Female, 45, French (Gypsy)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000132

(Epistaxis, menorrhagia)

CaseHPOFreeText: Post-traumatic hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

Case1: Patient LM --very minimal info on this patient

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: αIIbβ3 expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: Gly418Asp

ClinVar: N/A

CAiD: CA399803552

gnomAD: N/A

Case3: Patient FLD

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: (G242D)

ClinVar: 2894

CAiD: CA115837

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucous membrane bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Minimal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.113del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940264

gnomAD: N/A

PreviouslyPublished: Reference number 30

Case29: Strasbourg 1

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Bruising HP:0000978

CaseHPOFreeText: Hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13555

CAiD: CA123228

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

PreviouslyPublished: Ref 46, 47

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A Not reported for this proband

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Undetectable for this patient

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399803552

gnomAD: N/A

PreviouslyPublished: Reference number 20 in this article

Case11: Patient Gypsy (found in the GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Blood transfusions required

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Decreased surface expression of GPIIIa and GPIIb

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/A

PreviouslyPublished: Reference number 22 in this article

Case23: Family I from GT database, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703

gnomAD: MAF in the Other population 0.0001385 https://gnomad.broadinstitute.org/variant/17-45360816-C-T

PreviouslyPublished: Reference number 28

Case1: Patient KW (this patient can be found in the GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225

(Epistaxis, gingival bleeding)

CaseHPOFreeText: Blood transfusions needed

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Surface expression of GPIIb/GPIIIa not reported for this patient

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: 4.5-KB DEL, EX2-9

LegacyVariant: N/A

ClinVar: 2890

CAiD: N/A

gnomAD: N/A

PreviouslyPublished: PMID: 1702098

Supplementary Table S1:

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: N/A

Supplementary Table S1:

Case45: GT52, Argentina/Brazil, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1:

Case25: GT28, French/Syrian, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Supplementary Table S1:

Case36: GT42, Canadian/Egypt, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2148dup (p.Leu717AlafsTer3)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940304

gnomAD: N/A

Supplementary Table S1:

Case34: GT40, Canadian/Pakistani, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.857T>A (p.Val286Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805011

gnomAD: N/A

Case21: (M13) Female, 10 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case7: (GT-7) Female, 57 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: <5% surface expression levels of αIIbβ3

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGB3

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

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

ClinVar: N/A

CAiD: CA291224669

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

Case14: (M6) Female, 37 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case11: (M3) Female, 12 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case20: (M12) Female, 39 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case13: (M5) Male, 9 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case19: (M11), Male, 63 years old, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets

Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)

CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

Case1: Patient ET, gender, age, and ethnicity is not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: "However, ET platelets exhibited a normal surface expression of a-granule thrombospondin" this is all of the information we are given in this article; however Reference 13 might mention more on the protein expression. However, access is not available for article 13 at this time.

PlateletAggregation: ET's platelets fail to aggregate in response to stimuli (the article does not state which agonists/stimuli and does not mention response to ristocetin)

CasePreviousTesting: Two regions of ITGB3 were selected for amplification and sequence analysis. The first region, corresponding to exonIII encodes a fragment from D96 to D179 and the second region corresponding to exon IV, encodes a fragment from M180 to D233.

Gene: ITGB3

Variant: (NM_000212.2:c.719G>A (p.Arg240Gln)

LegacyVariant: (p.Arg214Gln)

ClinVar: 13553

CAiD: CA123224

gnomAD: N/A

PreviouslyPublished: Patient ET may have been previously published in PMID: 2512684; however, access is not available to this article

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, 5 years old, South East Asian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Information given on paternal grandmother

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

CasePresentingHPOs: HP:0000978, HP:0000421

(Severe bruising, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

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

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

ClinVar: 381747 and 417951 and 569057

CAiD: CA16608466 and CA8602498 and CA8602901

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

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms are severe with pathogenic bleeding time (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1

PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned

CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.

Gene: ITGA2B

Variant: NM_000419.3:c.1752+2T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602969

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

Case#: 2 (16 y, male - brother of Case 1, symptom onset/pain+movement limitation 8 y, diagnosis 16y)

DiseaseAssertion: Scheie syndrome

FamilyInfo: Male patient born to consanguineous parents

CasePresentingHPOs: 0034337

CaseHPOFreeText: claw hands with flexion contractures; electroneurology showed bilateral signs of mild median nerve suffering.

CaseNotHPOs: HP:0000280; HP:0001510; HP:0000943

CaseNotHPOFreeText: no coarse face, growth failure, other joint involvement, evidence of dysostosis multiplex of other bones. Normal intelligence, ophthalmologic, hearing and echocardiography, brain MRI

CaseEnzymeAssay: 0.64 (umol/g/h)

CaseUrineGAGs:

CaseERT: Yes, after diagnosis at 16y CaseBMT:

Variant1:c.1189+4A>T

Variant1ClinVarID:

Variant1CAID: CA2586965965

Variant2: 1189+4A>T

Variant2ClinVarID:

Variant2CAID: CA2586965965

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case#: 3 (19 y, male - cousin of Cases 1 and 2, symptom onset/pain+movement limittion 12y, diagnosis 19y))

DiseaseAssertion: Scheie syndrome

FamilyInfo: Male patient born to consanguineous parents

CasePresentingHPOs:

CaseHPOFreeText: electroneurology showed bilateral signs of mild median nerve suffering.

CaseNotHPOs: 0034337;HP:0001510; HP:0000943

CaseNotHPOFreeText: no coarse face, growth failure, other joint involvement, evidence of dysostosis multiplex of other bones. Normal intelligence, ophthalmologic, hearing and echocardiography, brain MRI

CaseEnzymeAssay: 0.57 (umol/g/h)

CaseUrineGAGs:

CaseERT: Yes, after diagnosis at 19y

CaseBMT:

Variant1:c.1189+4A>T

Variant1ClinVarID:

Variant1CAID: CA2586965965

Variant2: 1189+4A>T

Variant2ClinVarID:

Variant2CAID: CA2586965965

AdditionalVariants:

ParentalGenotype:

PreviouslyPublished

Case: Patient D

DiseaseAssertion: VWD2N

FamilyInfo: Family 3

ParentalGenotype(s):

CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130, HP:0011871

CaseHPOFreeText: PTsec = 37.9, FVIII U/dL = 31.1, FVIII ratio = 0.33, VWF:Ag U/dL = 95.0, VWF:FVIIIB U/dL = 23.8, VWF:FVIIIB ratio = 0.25, VWF:CB U/dL = 101.6, VWF:RCo U/dL = 112.4, RIPA % = 73.4, PlatVWF:Ag U/dL = 87.2

CaseNOTHPOs:

CaseNOTHPOFreeText: n/a

CasePreviousTesting: n/a

GenotypingMethod: "Genetic analysis was performed on exons 17-20 of the VWF gene as previously described" (PMID: 12393698)

PreviouslyPublished: n/a

Gene: VWF

Variant: c.2561G>A (p.Arg854Gln); homozygous

HGVS: NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/?new_evidence=false

CAID: n/a

gnomAD: MAF (European, Finnish) = 0.005692; https://gnomad.broadinstitute.org/variant/12-6143978-C-T

Case: Patient C

DiseaseAssertion: VWD2N

FamilyInfo: Family 2

ParentalGenotype(s):

CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130, HP:0011871

CaseHPOFreeText: PTsec = 38.0, FVIII U/dL = 37.6, FVIII ratio = 0.26, VWF:Ag U/dL = 146.2, VWF:FVIIIB U/dL = 34.0, VWF:FVIIIB ratio = 0.20, VWF:CB U/dL = 157.5, VWF:RCo U/dL = 137.4, RIPA % = 87.9, PlatVWF:Ag U/dL = 102.7

CaseNOTHPOs:

CaseNOTHPOFreeText: n/a

CasePreviousTesting: n/a

GenotypingMethod: "Genetic analysis was performed on exons 17-20 of the VWF gene as previously described" (PMID: 12393698)

PreviouslyPublished: n/a

Gene: VWF

Variant: c.2561G>A (p.Arg854Gln); homozygous

HGVS: NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/?new_evidence=false

CAID: n/a

gnomAD: MAF (European, Finnish) = 0.005692; https://gnomad.broadinstitute.org/variant/12-6143978-C-T

Case: Patient A

DiseaseAssertion: VWD2N

FamilyInfo: Family 1

ParentalGenotype(s):

CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130, HP:0011871

CaseHPOFreeText: PTsec = 35.2, FVIII U/dL = 18.5, FVIII ratio = 0.29, VWF:Ag U/dL = 62.9, VWF:FVIIIB U/dL = 10.7, VWF:FVIIIB ratio = 0.17, VWF:CB U/dL = 53.3, VWF:RCo U/dL = 60.4, RIPA % = 74.7, PlatVWF:Ag U/dL = 90.4

CaseNOTHPOs:

CaseNOTHPOFreeText: n/a

CasePreviousTesting: n/a

GenotypingMethod: "Genetic analysis was performed on exons 17-20 of the VWF gene as previously described" (PMID: 12393698)

PreviouslyPublished: n/a

Gene: VWF

Variant: c.2561G>A (p.Arg854Gln); homozygous

HGVS: NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/?new_evidence=false

CAID: n/a

gnomAD: MAF (European, Finnish) = 0.005692; https://gnomad.broadinstitute.org/variant/12-6143978-C-T

Case: Patient B

DiseaseAssertion: VWD2N

FamilyInfo: Family 2

ParentalGenotype(s):

CasePresentingHPOs: HP:0012147, HP:0030129, HP:0030130, HP:0011871

CaseHPOFreeText: PTsec = 37.2, FVIII U/dL = 36.7, FVIII ratio = 0.33, VWF:Ag U/dL = 109.8, VWF:FVIIIB U/dL = 25.7, VWF:FVIIIB ratio = 0.23, VWF:CB U/dL = 133.8, VWF:RCo U/dL = 94.5, RIPA % = 75.8, PlatVWF:Ag U/dL = 95.4

CaseNOTHPOs:

CaseNOTHPOFreeText: n/a

CasePreviousTesting: n/a

GenotypingMethod: "Genetic analysis was performed on exons 17-20 of the VWF gene as previously described" (PMID: 12393698)

PreviouslyPublished: n/a

Gene: VWF

Variant: c.2561G>A (p.Arg854Gln); homozygous

HGVS: NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/?new_evidence=false

CAID: n/a

gnomAD: MAF (European, Finnish) = 0.005692; https://gnomad.broadinstitute.org/variant/12-6143978-C-T

Case: 26, M, 24, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

7683delT (FS), Exon 45, Homozygous

Case: 19, F, 11, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): 2, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

2116C→T (Gln706X), Exon 16, Homozygous

Case: 20, F, 20, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

3931C→T (Gln1311X), Exon 28, Homozygous

3951C→T (Ala1317Ala)

Note: Mutation Gln1311X is likely due to a gene conversion; both mutations match the pseudogene sequence

Case: 11, M, 48, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

6182delT (FS), Exon 36, Homozygous

Case: 1, F, 38, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

276delT (FS), Exon 4

2157delA (FS), Exon 16

Homozygous

Case: 16, F, 16, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): 1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

1093C→T (Arg365X), Exon 9, Homozygous

Case: 34, M, 15, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: No

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

7300C→T (Arg2434X), Exon 43, Homozygous

Note: It is possible that the homozygous zygosity was detected from a PCR artifact (e.g. presence of a large gene deletion or point mutation that prevents amplification); different sets of primers were used, providing conformation and excluding the possibility for a PCR artifact due to point mutation.

Case: 24, F, 17, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): 1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

6520T→G (Cys2174Gly), Exon 37, Homozygous

Case: 12, F, 15, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no

ParentalGenotype:

2748delHYC was confirmed to be in both parents

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

8241del9, 2748delHisTyrCys, Exon 51, Homozygous

Case: 13, M, 8, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

139G→C (Asp47His), Exon 3, Homozygous

Case: 31, M, 32, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant: 7130insC (FS), Exon 42, Homozygous

Case: 21, F, 52, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: 10

CasePreviousTesting: n/a

Gene: VWF

Variant:

4036C→T (Gln1346X), Exon 28, Homozygous

Note: One unit (U) of alloantibody to VWF is the concentration that binds 50% of the VWF added to the system, with the total potency calculated as the reciprocal of the dilution containing 1 anti-VWF U (total U).

Case: 9, M, 34, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

3108+5G→A (Intronic), Exon 23, Homozygous

Note: Article assumes that 3108+5G→A is a frameshift mutation. No potential splice site mutation was confirmed at the mRNA level; “Splice Site Prediction program” found all mutations likely to disrupt normal splicing. No possible splice site mutation could be identified on 100 chromosomes from a group of 50 normal subjects with same genetic background as patients, excluding the possibility that these mutations represent common polymorphisms.

Case: 32, M, 30, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: No

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

7130insC (FS), Exon 42, Homozygous

Note: It is possible that the homozygous zygosity was detected from a PCR artifact (e.g. presence of a large gene deletion or point mutation that prevents amplification); different sets of primers were used, providing conformation and excluding the possibility for a PCR artifact due to point mutation.

Case: 25, M, 20, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): 1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

7674insC (FS), Exon 45, Homozygous

Case: 28, M, 25, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Mild

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

421G→A (Asp141Asn), Exon 5, Homozygous

Case: 29, M, 16, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

1117C→T (Arg373X), Exon 10, Homozygous

Case: 17, M, 19, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): 2, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

1110-1G→A (intronic), Exon 10, Homozygous

Note: Article assumes 1110-1G→A would be a frameshift mutation. No potential splice site mutation was confirmed at the mRNA level; “Splice Site Prediction program” found all mutations likely to disrupt normal splicing. No possible splice site mutation could be identified on 100 chromosomes from a group of 50 normal subjects with same genetic background as patients, excluding the possibility that these mutations represent common polymorphisms.

Case: P41, Chinese, female, 13yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 18; VWF:Ag (%) = 1.6, VWF:RCo (%) = 1.5, FVIII:C (%) = 2.8, VWF:CB (%) = 1.7, VWFpp (%) = 1.3, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 1.8

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.2547-13T>A - Unregistered Variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: P35, Chinese, female, 60yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 20; VWF:Ag (%) = 1.5, VWF:RCo (%) = 1.3, FVIII:C (%) = 3.1, VWF:CB (%) = 1.1, VWFpp (%) = 1.3, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.7, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 2.1

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.5870delA - unregistered variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: P37, Chinese, male, 20yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 10; VWF:Ag (%) = 0.6, VWF:RCo (%) = 0.5, FVIII:C (%) = 5.7, VWF:CB (%) = 0.6, VWFpp (%) = 0.7, VWF:RCo/VWF:Ag = 0.8, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 1.2, FVIII:C/VWF:Ag = 9.5

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.1025_1032dup - unregistered variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: P21, Chinese, male, 14yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 13; VWF:Ag (%) = 0.5, VWF:RCo (%) = <0,5, FVIII:C (%) = 2.3, VWF:CB (%) = <0.5, VWFpp (%) = <0.5, VWF:RCo/VWF:Ag = NA, VWF:CB/VWF:Ag = NA, VWFpp/VWF:Ag = NA, FVIII:C/VWF:Ag = 0.6

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.2568G>A (p.Trp856Ter)

HGVS: NM_000552.5:c.2568G>A (p.Trp856Ter)

ClinVarID: NA

CAID: CA383520212; http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA383520212

gnomAD: absent

Variant 2: c.4444_4445delinsG - unregistered variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: 83, M, 13 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 2, VWF:Ag (U/dl): <1, Bleeding Score: 6

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1812C>A (p.Tyr604*), Exon 15, Homozygous

Case: 5, F, 49 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no, family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): <1, Bleeding Score: 13

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1093C>T (p.Arg365*), Exon 9, Homozygous

Case: 7, F, 4 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): <1, Bleeding Score: 24

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1117C>T (p.Arg373*), Exon 10, Homozygous

Case: 67, M, 13 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: family history of disease, Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): 2.6, Bleeding Score: 7

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3686T>G (p.Val1229Gly), Exon 28

c.3692A>C (p.Asn1231Thr), Exon 28

c.3931C>T (p.Gln1311*), Exon 28

Homozygous

Case: 24, F, 0.8 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 2.4, VWF:Ag (U/dl): 2, Bleeding Score: 3

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1693C>T (p.Gln565*), Exon 14, Homozygous

Case: 32, M, 18 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: no family history of disease, Consanguinity: no

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 3.2, VWF:Ag (U/dl): <1, Bleeding Score: 12

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.2908delC (p.Leu970del), Exon 22, Homozygous

Case: 30, M, 1.1 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): <1, Bleeding Score: 4