Case20: GT16, Female, India, age of onset is 11 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Case36: GT60-2, Female, India, age of onset is 25 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Case26: GT33, Female, India, age of onset is 18 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Case24: GT25, Female, India, age of onset is 5 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.921C>A (p.Tyr307Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025209

gnomAD: N/A

Case14: GT03, Female, India, age of onset is 6 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.166-14C>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622881

gnomAD: MAF in the South Asian population is 0.00003274 https://gnomad.broadinstitute.org/variant/17-45360706-C-A

Case30: GT42, Female, India, age of onset is 26 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622925

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

Case23: GT21, Male, India, age of onset is 33 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.921C>A (p.Tyr307Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025209

gnomAD: N/A

Case35: GT60-1, Female, India, age of onset is 27 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

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

Case19: GT11, Female, India, age of onset is 12 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.115T>G (p.Cys39Gly)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400031666

gnomAD: N/A

Case15: GT04, Female, India, age of onset is 11 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Menorrhagia HP:0000132

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.356G>A (p.Arg119Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8622925

gnomAD: MAF in the Other population is 0.0001385 https://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the African population is 0.0002470 https://gnomad.broadinstitute.org/variant/17-45360910-G-A

Case16: GT07, Male, India, age of onset is 3 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.153del (p.Trp51CysfsTer5)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940728

gnomAD: N/A

Case34: GT55, Male, India, age of onset is 21 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

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

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

Gene: ITGB3

Variant: NM_000212.2:c.921C>A (p.Tyr307Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025209

gnomAD: N/A

PMID: 16463284

Gene: ITGA2B and ITGB3

HGNC: 6156 and 6156

PMID: 14687991

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

PreviouslyPublished: All probands in this article have been previously published in PMID: 12083483 therefore this paper is not being curated

Case1: (Patient TK) Male, 5 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The (p.His280Pro) mutation was inherited from his mother and the (p.Gly579Ser) mutation was inherited from his father

CasePresentingHPOs: N/A

CaseHPOFreeText: All patients (3 in this study) had suffered from a bleeding diathesis since early childhood

CaseNotHPOs: NA

ProteinExpression: The surface expression of the alphaIIbbeta complex on the patients' platelets was quantitated by flow cytometry. The level of antigen expression for TK was 19.9%

Platelet Aggregation: Absent platelet aggregation in response to ADP, collagen, and epinephrine, but normal platelet agglutination in response to ristocetin

CasePreviousTesting: The nucleotide sequences of the aIIb and b3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA

Gene: ITGB3

Variant: NM_000212.2:c.917A>C (p.His206Pro) and NM_000212.2:c.1813G>A (p.Gly605Ser) (See Table 1 to see zygosity statement, "double heterozygote for both variants")

LegacyVariant: (p.His280Pro) and (p.Gly579Ser)

ClinVar: N/A

CAiD: CA291224999 and CA291227621

gnomAD MAF in the East Asian population for (p.His206Pro) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45364575-A-C and MAF in East Asian population for (p.Gly605Ser) is 0.00005437 https://gnomad.broadinstitute.org/variant/17-45376796-G-A

PMID: 15583747

Gene: ITGB3

HGNC: 6156

PMID: 10233432

Gene: ITGB3

HGNC: 6156

Note: Other GT variants are mentioned at the end of the article; however, those have been mentioned in other papers-- and probands with those mentioned variants are not apart of this paper

PMID: 14629479

Gene: ITGB3

HGNC: 6156

PMID: 9012651

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report

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

DiseaseAssertion: Glanzmann thrombasthenia

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

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032647

gnomAD: N/A

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

Variant: NM_000212.2:c.1543del (p.Ser513fs)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500651429

gnomAD: N/A

Case43: (GT-53) 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

Case10: (GT-12) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT11 -GT14 are related to GT-12 see Table 1

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: not available (See Supplemental 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

Case18: (GT-20) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT19 are related to GT-20 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

Case17: (GT-19) Male, carrier status, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-19 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

Case53: (GT-72) Gender, age, or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGB3

Variant: NM_000212.2:c.662C>T (p.Thr221Met)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623017

gnomAD: MAF in European Finnish population 0.0001386 http://gnomad.broadinstitute.org/variant/17-45363673-C-T

Case14: (GT-16) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-16 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

Case42: (GT-52) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT49-GT52 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 East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

PMID: 20142940

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a case report of a 9 year old GT patient who presented with gum bleeding; however, no specific variants in ITGA2B and/or ITGB3 are presented in this patient; therefore we have insufficient evidnece

Supplementary Tables 1 and 2 combined information:

Case25: GT25, Female, 26 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

(Epistaxis, gingival bleeding, menorrhagia, infertility)

CaseHPOFreeText: Rupture of corpus luteum

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400029525

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case41: GT41, Male, 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 10-20% of αIIbβ3 expression measured by flow cytometry

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1736G>A (p.Trp579Ter) and NM_000212.2:c.1784_1802delinsGTCACA

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032429 (p.Trp579Ter) and CA915940255 (c.1784_1802delinsGTCACA)

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case33: GT33, Female, 12 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 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: ITGB3

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

LegacyVariant: N/A

ClinVar: 13553

CAiD: CA123224

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case23: GT23, Female, 11 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, HP:0000225, HP:0000132

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Platelet aggregation showed 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: ITGB3

Variant: NM_000212.2:c.1980C>A (p.Tyr660Ter) and NM_000212.2:c.2147G>T (p.Gly716Val)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032983 (p.Tyr660Ter) and CA400033923 (p.Gly716Val)

gnomAD: N/A

PMID: 16217260

Genes: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a proband with GT; however, no variants in ITGA2B and/or ITGB3 are mentioned therefore we have insufficient evidence

Table 3 Molecular Diagnosis of Patients with Glanzmann Thrombasthenia:

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

DiseaseAssertion: Glanzmann thrombasthenia type II

FamilyInfo: Segregation analysis confirmed in presence of heterozygous mutations in this proband.

ParentalGenotype: Although segregation analysis confirmed, we do not know which variant in particular came from mom or dad.

CasePresentingHPOs: N/A

CaseHPOFreeText: Patients presented with a variable bleeding diathesis; most patients had epistaxis (54%), cutaneous bleeding (58%), and menorrhagia (100% of women) while other common symptoms (oral cavity, GI, following dental extraction of mild injuries, postpartum, or hematomas) were in general milder. There is no specific phenotypes attached to probands in this paper.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: There was severely impaired aggregation in response to all physiological agonists, and ristocetin induced platelet agglutination was normal or reduced to some extent.

CasePreviousTesting: Total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Then, using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing. Every mutation found in cDNA was confirmed in DNA samples.

Gene: ITGB3

Variant: NM_000212.2:c.448A>G (p.Met124Val) and NM_000212.2:c.774_775del (p.Cys258Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622961 and CA915940285

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

Case31: (GT41) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.887_901del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA626379036

gnomAD MAF in the South Asian population is 0.00003266 https://gnomad.broadinstitute.org/variant/17-45364541-AATGACGGGCAGTGTC-A

PMID: 19691478

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

Case12: (GT39) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.92G>A (p.Cys31Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400031593

gnomAD N/A

Case28: (GT30) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Mother and father are heterozygous for the mutation

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.674del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940689

gnomAD N/A

Case20: (GT10)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.59T>C (p.Leu20Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400028389

gnomAD N/A

Case17: (GT72) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1641C>G (p.Cys547Trp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400030171

gnomAD N/A

Case30: (GT31) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.887_901del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA626379036

gnomAD MAF in the South Asian population is 0.00003266 https://gnomad.broadinstitute.org/variant/17-45364541-AATGACGGGCAGTGTC-A

PMID: 17250517

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions two GT case reports of girls with menorrhagia; however, there was no mention of variants in ITGA2B and/or ITGB3; therefore there is insufficient evidence

Supplementary Table S1 & S2 Proband and Variant Information:

Case60: GT62, Female, 58 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister (that is all the information we are given)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000225, HP:0000132, HP:0006298

(Easy bruising, gingival bleeding, menorrhagia, bleeding after dental extraction)

CaseHPOFreeText: Esophageal bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.31T>C (p.Trp11Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291240306

gnomAD: N/A

PMID: 25728920

Genes: ITGA2B and ITGB3

HGNC: 6138 and 6156

Note: In the annotations, case #'s don't always match up with the exact proband #, because not all probands had GT variants identified in them

Supplementary Table S1 & S2 Proband and Variant Information:

Case31: GT35a, Female, 18 years old, USA

DiseaseAssertion: Glanzmann thrombasthenia

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

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B and ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

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

Supplementary Table S1 & S2 Proband and Variant Information:

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

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622925 and CA400032338

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case48: GT48, Male, 10 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000421, HP:0001934

(Ecchymosis, epistaxis, persistent bleeding after trauma)

CaseHPOFreeText: Frequent hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: No serious episode of spontaneous bleeding

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

PlateletAggregation: N/A (Not available for this proband see Supp Table S1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.1094A>G (p.Asn365Ter) and NM_000212.2:c.1522del (p.Gln508Serfs*161)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400026292 and CA772541579

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case69: GT73, Female, 34 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Ecchymosis, epistaxis, gingival bleeding, menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed nromal to reduced 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.889G>A (p.Gly297Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623074

gnomAD: MAF in the European (non-Finnish) population is 0.00002643 https://gnomad.broadinstitute.org/variant/17-45364547-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case1: GT1, Male, 9, French/African

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0011890, HP:0000421, HP:0000225

(Bruising susceptibility, prolonged bleeding following procedure, epistaxis, gingival bleeding)

CaseHPOFreeText: Tonsilar hemorrhage

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.1913+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032825

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967, HP:0030137

(Epistaxis, purpura, ecchymosis, petechiae, prolonged bleeding at 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: 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:

Case44: GT43b, Male, 11 years old, Morrocan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister is 43a (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000979, HP:0031364, HP:0000967

(Epistaxis, purpura, ecchymosis, petechiae)

CaseHPOFreeText: Lots of bleeding at circumcision

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:

Case51: GT51, Male, 29 years old, French/African

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421 (Epistaxis)

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.861del (p.Arg287Serfs * 34) and NM_000212.2:c.1456del (p.Cys486Alafs * 183)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940375 and CA915940376

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case58: GT60, Male, 54 years old, French/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000978, HP:0002239, HP:0000225

(Epistaxis, easy bruising, GI bleeding, 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: ITGB3

Variant: NM_000212.2:c.1801T>C (p.Cys601Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623361

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

PMID: 11588040

Gene: ITGB3

HGNC: 6156

PMID: 30388316

Gene: ITGA2B and/or ITGB3 (Proband presented with GT therefore these two genes may be involved)

HGNC: 6138 and 6156

InsufficientEvidence: Proband with Glanzmann thrombasthenia presented in this article; however, no variant information provided

Case2: Female, Spanish, 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: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025814

gnomAD: N/A

Case5: Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

Variant: NM_000212.2:c.892C>G (p.Gln298Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025097

gnomAD: N/A

Case12: 2 Females, age not specified "Two sisters" is what the Table mentions

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002239

(Gastrointestinal bleeding)

CaseHPOFreeText: Life threatening bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

CasePreviousTesting:

Gene: ITGB3 and ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

gnomAD: MAF in the African population 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C , MAF in Latino population 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A and MAF in Latino population 0.0001903 (p.Arg775Gln)

Case24: Male, age not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding (See Table 1 for Clinical and Biological Data-- minimal information)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

Variant: NM_000212.2:c.1619G>A (p.Gly540Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400030071

gnomAD: N/A

Case10 : Female, age not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asp314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

gnomAD: N/A

Case23: Female, age not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: Minimal information, not specific enough

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

Gene: ITGB3

Variant: All Table 1 states is "missense mutation" not enough information provided

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Case22: Female, 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: Minimal information, not specific enough

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

Gene: ITGB3

Variant: NM_000212.2:c.166-2A>G (IVS2-2A>G)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224483

gnomAD: N/A

PMID: 14508803

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions GT patients however no variants in ITGA2B and/or ITGB3 are mentioned in these patients.

In this study the goal was to determine what the common subtype of GT was: The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians

Case#: GT3 male, 17 years old

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: (found in appendix) HP:0001892, HP:0000421, HP:0000225, HP:0000967, HP:0000979, HP:0031364, HP:0006298

ExpressionEvidence: Flow Cytometry of platelet αIIbβ3: 0%CD41, .43% CD61

FamilyInfo: Positive consanguinity

GenotypingMethod: Sanger DNA sequencing to identify causative mutations in each case

ClinVar: 1691476

CAID: CA400030171

Variant: NM_000212.3:c.1641C>G

GnomAD: Not Found

Case#: GT2 male, 7 years old

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: (found in appendix) HP:0000967, HP:0000979, HP:0031364, HP:0000978, HP:0002239

ExpressionEvidence: Flow Cytometry of platelet αIIbβ3: 0%CD41, 0% CD61

FamilyInfo: Positive consanguinity

GenotypingMethod: Sanger DNA sequencing to identify causative mutations in each case

ClinVar: 1691476

CAID: CA400030171

Variant: NM_000212.3:c.1641C>G

GnomAD: Not Found

Case30: Patient CM

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

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

(Epistaxis, gingival bleeding, menorrhagia)

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.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: Reference 48 and 49

Case32: Patient SH

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 20% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.725G>A (p.Arg242Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224896

gnomAD: N/A

PreviouslyPublished: Reference number 5 in this article

Case33: Patient GT3

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.777+1G>A and the second variant I am not sure how to write out

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623036

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

PreviouslyPublished: References 53-55

Case38: Patient IJ12

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000421, HP:0000225, HP:0002239, HP:0000979, HP:0000967, HP:0006298

(Epistaxis, gingival bleeding, GI bleeding, purpura/petechiae, prolonged bleeding after tooth extraction)

CaseNotHPOsFreeText: N/A

ProteinExpression: <2% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.2031_2041del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940605

gnomAD: N/A

PreviouslyPublished: References 8-12

Case28: Patient PDJ

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.709_710del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623029

gnomAD: MAF in the European non Finnish population is 0.00001796 https://gnomad.broadinstitute.org/variant/17-45363717-CAG-C

PreviouslyPublished: Reference 45

Supplementary Table S1:

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8623443

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

Supplementary Table S1:

Case6: GT7, French, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 631774

CAiD: CA8622892 and CA291224658

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

Supplementary Table S1:

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

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940309

gnomAD: N/A

Supplementary Table S1:

Case8: GT9, French, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.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 is 0.00006482 https://gnomad.broadinstitute.org/variant/17-45363676-T-C

Supplementary Table S1:

Case43: GT50, French, age and gender not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623200

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

Supplementary Table S1:

Case51: GT60, 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.1801T>C (p.Cys601Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623361

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

Supplementary Table S1:

Case53: GT62, French, gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.31T>C (p.Trp11Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291240306

gnomAD: N/A

Supplementary Table S1:

Case26: GT30, "USA"-what the supp table states, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623036

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

Supplementary Table S1:

Case37: GT43a, Morrocco, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.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 https://gnomad.broadinstitute.org/variant/17-45363694-G-A

Supplementary Table S1:

Case1: GT1, French/African, Gender or age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

Variant: NM_000212.2:c.1913+1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400032825

gnomAD: N/A

Supplementary Table S1:

Case11: GT12, French, age and gender not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224669

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

PMID: 9694297

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence

PMID: 28299211

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions cases of patients with Glanzmann thrombasthenia and their phenotypes; however, no mention of variants in ITGB3 or ITGA2B

Case14: Patient ID N, Male, 7 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967, HP:0000979, HP:0000978, HP:0004406, HP:0000225

(Petechiae, purpura, easy bruising, recurrent epistaxis, gingival bleeding)

CaseHPOFreeText: Hemorrhage after dental, hemorrhage after trauma

CaseNotHPOs: HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(GI bleeding, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Ear bleeding

ProteinExpression: N/A

PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin

CasePreviousTesting: Exon PCR was used to amplify coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available

Gene: ITGB3

Variant: NM_000212.2:c.774T>A (p.Cys258Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023704

gnomAD: N/A

PMID: 8126100

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention GT probands or variants in ITGA2B and ITGB3. In this study, researchers have examined the talin phosphorylation and proteolytic cleavage as possible mechanisms by which talin's subcellular distribution could be regulated in platelets.

Case1: (M.S) Female, 19 years old, Caucasian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The mutation has been inherited from proband's parents who are heterozygous for the same mutation the proband has.

CasePresentingHPOs: HP:0000978 (Bruising)

CaseHPOFreeText: Intracerebral hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Fig 4 for flow cytometry analysis of protein expression

PlateletAggregation: Absence of platelet aggregation in response to all agonists tested i.e. ADP, collagen, platelet activating factor acether thrombin, and arachidonic acid; however, ristocetin induced platelet aggregation was normal

CasePreviousTesting: Sequenced patient's GPIIIa exons encompasing a highlight conserved reion of GPIIIa.

Gene: ITGB3

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

LegacyVariant: (p.Arg214Trp)

ClinVar: 13555

CAiD: CA123228

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

PMID: 1602006

Gene: ITGB3

HGNC: 6156

PMID: 18200593

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a 27 year old proband with Glanzmann thrombasthenia; however, no variants in ITGA2B and/or ITGB3 were mentioned in this proband therefore we have insufficient evidence

PMID: 15219201

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

PMID: 9074427

Gene: ITGA2B

HGNC 6156

PreviouslyPublished:The proband in this article is from PMID: 2180491 and the variant this proband has is from PMID: Not available, (Bourre et al. 1990)

PMID: 30756012

Gene: ITGA2B and/or ITGB3 (Patient has GT; therefore, these two genes may be implicated)

HGNC: 6138 and 6156

InsufficientEvidence: Case report presented here; however, no mention of variants in ITGA2B or ITGB3.

Case#: half a year old, male

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, 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

Allele 1:

ClinVar: 996164

CAID: CA400023596

Variant: NM_000212.3:c.724C>T

GnomAD: Highest in European (Non-Finnish) 0.00006483 (1/15426)

Allele 2

ClinVar: Not found

CAID: CA626684825

Variant: NM_000212.3:c.225_226del

GnomAD: East Asian highest at rate of 0.0001087 2/18394

ExpressionEvidence: Flow Cytometry of platelet integrin: .3% B3 expression, .6% A2B expression

PMID: 1412224

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This mentions 2 Glanzmann thrombasthenia patients; however, no variants in ITGA2B and/or ITGB3 are mentioned in the patients. The purpose of this study was to investigate fibrinogen binding to the platelet receptor in normal subjects, patients with GT, and carriers of this disorder, s well as in patients with chronic uremia before and after treatment with recombinant erythropoiten.

Case21: Patient GI, gender and age are not specified, all of these patients are Caucasian (either Italian or European)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1

PlateletAggregation: See Table 1

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

Gene: ITGB3

Variant: c.728T>T (Unregistered) GT database has the same variant listed and it won't show up in CAR

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^