Case1: Patient F1P1, Male, 11 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0000978

(Gingival bleeding, easy bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGB3

Variant: NM_000212.2:c.176T>C (p.Leu59Pro) and NM_000212.2:c.1143A>C (p.Val381Val) and NM_000212.2:c.1545G>A (p.Arg515Arg) and the other variant stated here is g.41037G>C which I am marking as an Unknown Variant-- biocurator should look at this and determine variant

LegacyVariant: N/A

ClinVar: 13558 (p.Leu59Pro), 255535 (p.Val381Val), 255537 (p.Arg515Arg)

CAiD: CA123235 (p.Leu59Pro), CA8623175 (p.Val381Val), CA8623284 (p.Arg515Arg)

gnomAD: MAF in the Ashkenazi Jewish population is 0.1565 https://gnomad.broadinstitute.org/variant/17-45360730-T-C for (p.Leu59Pro) and MAF in the East Asian population is 0.5857 https://gnomad.broadinstitute.org/variant/17-45368337-A-C for (p.Val381Val) and MAF in the East Asian population for (p.Arg515Arg) is 0.3455 https://gnomad.broadinstitute.org/variant/17-45369789-G-A

Case3: Patient F3P1, Male, 26 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygous for this mutation

CasePresentingHPOs: HP:0000225, HP:0004406, HP:0000978,HP:0000790, HP:0002239

(Gingival bleeding, recurrent epistaxis, easy bruising, hematuria, GI bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case4: Patient F4P1, Male, 43 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0004406 (Recurrent epsitaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B and ITGB3

Variant: ITGA2B variants: g.13378A>C, g.14856C>A, g.19021C>T (I am denoting this as Unknown Variants as I need guidance with these-- biocurator curating this paper can also look them up- but I am noting them here) and ITGB3 variants: NM_000212.2:c.176T>C (p.Leu59Pro) and NM_000212.2:c.1143A>C (p.Val381Val) and NM_000212.2:c.1545G>A (p.Arg515Arg)

LegacyVariant: N/A

ClinVar: 13558 (p.Leu59Pro), 255535 (p.Val381Val), 255537 (p.Arg515Arg)

CAiD: CA123235 (p.Leu59Pro), CA8623175 (p.Val381Val), CA8623284 (p.Arg515Arg)

gnomAD: MAF in the Ashkenazi Jewish population is 0.1565 https://gnomad.broadinstitute.org/variant/17-45360730-T-C for (p.Leu59Pro) and MAF in the East Asian population is 0.5857 https://gnomad.broadinstitute.org/variant/17-45368337-A-C for (p.Val381Val) and MAF in the East Asian population for (p.Arg515Arg) is 0.3455 https://gnomad.broadinstitute.org/variant/17-45369789-G-A

Case1: Patient F1P1, Male, 11 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygous for mutation

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Case2: Patient F2P1, Male, 34 years old, Tunisian

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Table 1 states there is a family history of bleeding (we have minimal to no specific info on this)

ParentalGenotype: Mother and father are heterozygotes for the mutation here

CasePresentingHPOs, : HP:0000225, HP:0004406, HP:0000978,HP:0000790

(Gingival bleeding, recurrent epistaxis, easy bruising, hematuria)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: GT diagnosis was based on absent platelet aggregation induced by ADP, collagen, and TRAP and subnormal or cyclical ristocetin induced agglutination

CasePreviousTesting: Using PCR they successfully amplified 20 DNA fragments for the ITGA2B gene (covering more than 48% of the ITGA2B gene constituting 30 exons) and15 DNA fragments of theITGB3gene (covering 15 exons)

Gene: ITGA2B

Variant: NM_000419.3:c.2702C>A (p.Ser901X) another variant this patient has is g.13944G>A --> I am noting this as Unknown Variant as I will need guidance curating this one

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399792888

gnomAD: N/A

Supplementary Table S1:

Case47: GT54, Arg/Italian, 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.2014+5G>A and the other variant is a "LR deletion" which is all thats mentioned

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940701

gnomAD: N/A

Supplementary Table S1:

Case58: GT, French, gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and other other variant is stated as "LR deletion" so I will note it as an Unknown Variant

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290950376

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

Supplementary Table S1:

Case39: GT45, French, age and gender not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.551_626del (p.Arg184_Gln208del) and the other variant is noted as "LR deletion" and that is all the information we are given so I will note it as an Unknown Variant

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940373

gnomAD: N/A

Case20: Patient TE, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: Article states, "heterozygous parents of TE"

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

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

Gene: ITGB3

Variant: NM_000212.2:c.856G>A (p.Gly286Arg) and the variant is c.1129Ains --> NM_000212.2:c.1129dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020688 and CA915940291

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

Case11: Patient WV, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

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

Gene: ITGA2B

Variant: c.2232Gins (Noting this as an Unknown Variant as this won't show up in CAR-- I am sure there is a way to retrieve the CAiD; however, will need to discuss with senior biorcurator)

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

Case10: Patient WC, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

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

Gene: ITGA2B

Variant: c.2232Gins (Noting this as an Unknown Variant as this won't show up in CAR-- I am sure there is a way to retrieve the CAiD; however, will need to discuss with senior biorcurator)

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

Case21: Patient GI, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

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

Gene: ITGB3

Variant: NM_000212.2:c.1129dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940291

gnomAD: N/A

Supplemental Table S1:

Case24: N/A (from Turkey)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Individual clinical data not given

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

PreviouslyPublished: PMID: 25734216

Supplemental Table S1:

Case34: Female, Germany, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Moderate to severe bleeding that prompted transfusion

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: ^

gnomAD: ^

PreviouslyPublished: PMID: 20345392

Case1: Female, 35 day old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The proband’s mother and father carry heterozygous c.512delC and c.1686delG mutations, respectively. Other parameters for parents are shown in Table 1.

CasePresentingHPOs: HP:0031364, HP:0000967

(Ecchymosis, petechiae)

CaseHPOFreeText: Large parietal and cervical cephalohaematoma, severe anemia

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry of platelet surface antigens revealed the absence of the αIIbβ3 complex.

PlateletAggregation: Prolonged closure time at PFA-100, absent ADP, adrenaline, collagen induced platelet aggregation, and ristocetin induced platelet aggregation at the lower limit of normal

CasePreviousTesting: Sequencing of ITGA2B and ITGB3 genes showed that proband is compound het.

Gene: ITGA2B

Variant: Can not conclusively determine if c.481delC and c.1654delG are the variants intended by the authors based on the available information.

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD: N/A

Case2: Arab Patient (found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0002239, HP:0000132, HP:0000967, HP:0000979, HP:0006298

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <2% of normal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: IVS(-3)-418del (May be registered; however, need to consult senior biocurator)

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

PreviouslyPublished: References 8-12