PMID: 20438394

Gene: ITGB3

HGNC:6156

Case6: (GT-07) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-07 see Table 1

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

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case2: (GT-02) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-02 see Table 1

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

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: N/A for proband 2 (See Supplemental Table 3)

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940251

gnomAD: N/A

Case33: (GT-43) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT43-GT44 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B

Variant: NM_000419.3:c.1620G>C (p.Gln540His) and NM_000419.3:c.1616T>G (p.Leu539Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802407 and CA399802416

gnomAD: N/A

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

Case50: (GT-62) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Minimal information (See Supplementary Table 3)

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

Gene: ITGA2B and ITGB3

Variant: NM_000419.3:c.985G>T (p.Val329Phe) and NM_000212.2:c.1265G>A (p.Ser422Asn)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804719 (p.Val329Phe) and CA291225740 (p.Ser422Asn)

gnomAD: N/A

NM_017489:c.415+10->G

Unable to identify variant for following reasons: 1) NM_017489 is for TERF1 not ITGA2B 2) c.415 is not a exon boundary in ITGA2B Mane transcript 3) ->G is not standard notation, is this a substitution to G of whatever is normally there or is it an insertion of G or something else?

NM_000419:c.1947-9T>C

PMID: 29439184

Gene: ITGB3

HGNC: 6156

PMID: 15102025

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions "a platelet defect as a heterozygous Glanzmann thrombasthenia" however unable to access the article they cited after that sentence to get further information on the heterozygous variant

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:

Case56: GT57, Female, 10, Argentinian/European

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000967

(Epistaxis, petechia)

CaseHPOFreeText: Hematomas

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.571T>G (p.Phe191Val) and NM_000419.3:c.961G>T (p.Phe191Alafs*32)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805699 and CA399804768

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

(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

Case18: (M10) Female, 37, French Gypsy

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD N/A

PMID: 20492470

Gene: ITGA2B

HGNC: 6138

Case13: Female, 9 years old, Indian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002248, HP:0000421, HP:0031364 (Haematemesis, epistaxis, ecchymosis)

CaseHPOFreeText:

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.2674del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940582

gnomAD: N/A

Case12: Male, 3 years old, Indian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sibling is proband number 11 in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0002249, HP:0000421 (Melena, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802454

gnomAD: N/A

Supplementary Table S1:

Case29: GT34, USA, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8603038 and CA626121071

gnomAD: MAF in the European (non-Finnish) population is 0.000008790 https://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population for NM_000419.3:c.1946+3G>T is 0.000 https://gnomad.broadinstitute.org/variant/17-42456008-C-A

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:

Case21: GT24, French Gypsy, gender and age not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: 2895

CAiD: CA10575473

gnomAD: N/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

PMID: 11877352

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions GT patients and 2 variants in ITGA2B and/or ITGB3 that have been seen in these patients; however, there is no direct correlation for which patients harbor which variant; therefore there is insufficient evidence

"Five were homozygous for the 11-bp deletion in the β3 gene11 and 2 were homozygous for a splice site mutation of the αIIb gene"

Case7: Male, 1 years old, West Bengal India

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000225, HP:0006298, HP:0000967

(Gingival bleeding, prolonged bleeding after tooth extraction, petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 1 for values

PlateletAggregation: See Table 1 for values

CasePreviousTesting: PCR amplification of ITAG2B and ITGB3

Gene: ITGA2B

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

LegacyVariant: (p.Arg520Trp)

ClinVar: N/A

CAiD: CA399802348

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

PMID: 16879215

Gene: ITGA2B and ITBG3

HGNC: 6138 and 6156

PMID: 12163005

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article is a review on GT.

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

Case3: Gender or age not specified, Thai ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Parental information available in Table 2

ParentalGenotype: Father: p.Arg782Ter/WT and Mother: Unavailable

Note: No parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.

PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.

CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.

Gene: ITGA2B

Variant: NM_000419.3:c.2344C>T (p.Arg782Ter) and NM_000419.3:c.2915dup (p.Leu973Alafs*63)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399796586 (p.Arg782Ter) and CA8602531 (p.Leu973Alafs*63)

gnomAD: MAF for (p.Leu973Alafs*63) in East Asian population 0.0001088 http://gnomad.broadinstitute.org/variant/17-42452054-C-CG

Case2: Gender or age not specified, Thai ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Parental information available in Table 2

ParentalGenotype: Father: p.Val206Asp/WT and Mother: also p.Val206Asp/WT (See Table 2)

Note: Yes to parental consanguinity

CasePresentingHPOs: N/A

CaseHPOFreeText: The article does not mention specific bleeding phenotypes for each of the 4 probands in the article, rather, there is a general statement that says: "The common presentations included recurrent epistaxis, bleeding in oral cavity, and easy-bruising spontaneously or after trauma"

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinEpression: General statement from the article that states that flow cytometry to assess the surface GPIIb/IIIa complex showed reduced expression for all probands.

PlateletAggregation: The platelet aggregation test was typically defective with all physiological agonists except ristocetin, for all patients.

CasePreviousTesting: Whole exome sequencing was performed on the 30 exons of ITGA2B and 15 exons in ITGB3. PCR and direct sequencing were then performed in the DNA samples of the patients and their available parents to verify the presence of the identified mutations.

Gene: ITGA2B

Variant: NM_000419.3:c.617T>A (p.Val206Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805578

gnomAD: N/A

Supplementary Tables 1 and 2 combined information:

Case22: GT22, Female, 16 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

CasePresentingHPOs: HP:0000132 (Menorrhagia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: N/A

ClinVar: 2892

CAiD: CA115834

gnomAD: MAF in the East Asian population: 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A

Supplementary Tables 1 and 2 combined information:

Case4: GT4, Female, 22 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 no response to ADP and collagen but normal response to ristocetin

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602626

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

PMID: 31777146

Disease: Glazmann's Thrombasthenia type 1 and factor 7 deficiency

Case: 13 year old male, from non-consanguineous

CasePresentingHPOs: HP:0011889, HP:0000978, HP:0031364,

GenotypingMethod: Direct sequencing of all coding, splice site and promoter regions of F7 and ITGA2B and ITGB3 genes. Heterozygous for two ITGB3 variants predicted to be deleterious in silico.

First heterozygous mutation:

ClinVar: Not found

CAID: CA400022111

Variant: NM_000212.3:c.473A>T

GnomAD: Not found

Second heterozygous mutation:

ClinVar: Not found

CAID: CA400033092

Variant: NM_000212.3:c.2027A>C

GnomAD: Not found

PlateletAggregation: Platelet aggregation studies showed absent aggregation with adenosine diphosphate (ADP), collagen and was reduced with ristocetin

ExpressionEvidence: flow cytometry studies for platelet receptors showed absence of αIIbβ3 integrin and normal levels of GPIb and GPIX receptors

Case2: Male, 38 years old, Korean

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Figure 1 shows haplotype analysis

CasePresentingHPOs: HP:0004406, HP:0000225

(Recurrent epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analyses revealed markedly decreasedCD41/CD61 expression (<1%) in Patient 2 (type I GT).

PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists

CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623377

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

PMID: 28370369

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: No GT probands or variants within ITGA2B or ITGB3 mentioned in this article

Case12: Patient CW (can be found in GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000979, HP:0000967, (Ecchymosis, Purpura/petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <1% of normal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.480C>G (p.Ser160_102del)

LegacyVariant: N/A

ClinVar: 2892 (Arg584Ter)

CAiD: CA115834 and CA399805892

gnomAD: MAF in the East Asian population is 0.0002176 for the Arg584Ter variant and MAF in the East Asian population is 0.00005507 for the other variant https://gnomad.broadinstitute.org/variant/17-42463013-G-C

PreviouslyPublished: Reference number 23 in this article

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

PMID: 30819996

Gene: ITGA2B and/or ITGB3 (Proband has GT; therefore, one of these variants may be implicated)

HGNC: 6138 and 6156

InsufficientEvidence: Case report presented in this article with Glanzmann thrombasthenia; however, sequencing reveals differential diagnosis to GT, with mutations in other genes.

Case10: Patient ID J, Female, 5 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Related to Patient's I and K (See Table 1)

ParentalGenotype: N/A (Parents are consangenous)

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

(Easy bruising, recurrent epistaxis, gingival bleeding, GI bleeding

CaseHPOFreeText: Hemorrhage after trauma, hematoma

CaseNotHPOs: HP:0000967, HP:0000979, HP:0002239, HP:0000790, HP:0005261, HP:0002248

(Petechiae, purpura, intracranial hemorrhage, hematuria, hemarthrosis, hematemesis)

CaseNotHPOsFreeText: Hemorrhage after dental, 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: ITGA2B

Variant: NM_000419.3:c.1652G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602986

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

PreviouslyPublished: PMID: 19172520

PMID: 19138263

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions probands with GT; however, no mention of variants in ITGA2B and/or ITGB3

Note: Full-text found on UNC library website-- was not able to annotate on that document therefore annotation found here

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

Case13: Patient BM, 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: ITGA2B

Variant: NM_000419.3:c.2113T>C (p.Cys705Arg)

LegacyVariant: (p.Arg674Arg)

ClinVar: N/A

CAiD: CA8602816

gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G

Case19: Patient SM, 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: NM_000212.2:c.355C>T and NM_000212.2:c.1801T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622924 and CA8623361

gnomAD: MAF in the South Asian population is 0.0001307 https://gnomad.broadinstitute.org/variant/17-45360909-C-T and MAF in the European non Finnish pop is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C

PMID: 25373348

Genes: ITGA2B and ITGB3

HGNC: 6138 and 6156

Case3: Female, 32 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A per Table 1

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Prolonged ivy bleeding times, bleeding diathesis since early childhood

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Surface expression of αIIbβ3 was analyzed by flow cytometry which was 10-20% of normal

PlateletAggregation: Aggregation in response to ADP, epinephrine and collagen was absent but normal in response to ristocetin

CasePreviousTesting: Nucleotide sequences of the αIIb and β3 coding regions were determined by direct sequencing of RT-PCR products from platelet RNA.

Gene: ITGA2B

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

LegacyVariant: (p.Gln747Pro)

ClinVar: 225393

CAiD: CA290947544

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

PMID: 9576300

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: 10673707

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient; however, there is no mention of variants in ITGA2B and/or ITGB3; therefore, there is insufficient evidence

Case12: No assertion made on age, gender or ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The identified variants were heterozygote in parents.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.

Gene: ITGA2B

Variant: NM_000419.3:c.1555C>T (p.Gln519Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802559

gnomAD: N/A

Case1: Male, 8 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Sister had no bleeding tendency (all the information given in the previously published article cited in this annotation)

ParentalGenotype: Parental mutations shown in Fig. 3 A and B

CasePresentingHPOs: HP:0000421

(Epistaxis)

CaseHPOFreeText: Tonsilar bleeding

CaseNotHPOs: HP:0000979

(Purpura)

CaseNotHPOFreeText: N/A

ProteinExpression: Western blotting indicated that the proband's platelets contained no normal GPIIb, but showed a trace amount of an abnormal GPIIb (-6% with respect to the GPIIb level in a normal individual).

PlateletAggregation: Decreased aggregation in response to ADP, collagen and epinephrine but a normal ristocetin-induced aggregation (this information was obtained from the previously published article cited at in this annotation)

CasePreviousTesting: Genomic DNA fragments containing exons of the GPIIb gene were amplified by PCR

Gene: ITGA2B

Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) and NM_000419.3:c.2602-3C>G

LegacyVariant: N/A

ClinVar: 2892 and 2893

CAiD: CA115834 and CA10575472

gnomAD: MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A and MAF in the East Asian population is 0.00006523 https://gnomad.broadinstitute.org/variant/17-42453087-G-C

PreviouslyPublished: PMID: 1891767

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

Case9: (GT58), Gender, age and ethnicity not reported

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGA2B

Variant: NM_000419.3:c.1028T>C (p.Leu343Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399804619 (p.Leu343Pro)

gnomAD N/A

Case4: (GT69), Gender, age and ethnicity not reported

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

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

CaseNotHPOs: N/A

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

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

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

Gene: ITGA2B

Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro)

gnomAD N/A

Case23: (GT67) 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:

Variant: NM_000419.3:c.1919_1920del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940685

gnomAD N/A

PMID: 16793673

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions individuals with Glanzmann thrombasthenia; however, the probands don't have variants in ITGAB and/or ITGB3 mentioned

Case#: Female, 30 (age of diagnosis)

Disease: Glazmann's Thrombasthenia Like Syndrome

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

Gingival bleeding, Bruising susceptibility, Prolonged bleeding after dental extraction

CaseNotHPOs: NA

FamilyInfo: Pedigree figure 1. Father and two daughters affected.

PlateletAgreggation: Family member studied: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA, with normal ristocetin agglutination

GenotypingMethod: Genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.

ClinVar: Not Found

CAID: CA400034251

Variant: NM_000212.3:c.2236A>C (ITGB3)

GnomAD: Not Found

ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 38%, CD61 (GPIIIa) 41%, and CD42b (GPIb) 85%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).

Case26: (Proband CabGT-26), Female, age not specified, North American

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed 12% of both GPIIIa and GPIIb surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGB3

Variant: "c.1143C>A" is incorrect in the CAR- so will need a senior biocurator to ask-- and NM_000212.2:c.1260G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623200

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

Case25: (Proband CabGT-25), Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: N/A

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGB3

Variant: c.112513_112516del (Not showing up in the CAR) and they could not determine the second variant

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD N/A

PMID: 28161816

Gene: ITGA2B and ITGB3

HGNC 6138 and 6156

NoEvidence: The aim of this article's study was to evaluate the clinicopathological spectrum of this syndrome and to study the platelet glycoprotein IIb/IIIa complex and platelet antibodies by flow cytometry in a cohort of children with GT in a tertiary care center in Upper Egypt. There is no mention of individual probands with variants in ITGA2B or ITGB3

Case#: Female, 29 yo

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Figure 2 Father and brother, unaffected carriers. Mother, unaffected negative. Sister, affected: Epistaxis, Cutaneous bleeding, Menorrhagia, Hematuria, Postpartum bleeding, Other bleeding symptoms (Ruptured corpus luteum bleeding)

ParentalGenotype: Father carrier, unaffected. Mother negative, unaffected.

CasePresentingHPOs: HP:0000421, Epistaxis. HP:0000132, Menorrhagia. HP:0000790, Hematuria. HP:0003540, Impaired platelet aggregation. HP:0001892, Abnormal bleeding. HP:0003010, Prolonged bleeding time. HP:0034263, Abnormal vaginal bleeding.

PlateletAggregation: Normal platelet morphology, count 159 (125-350), MPV 10.6 fL (6.5-12.0), and PDW 12% (19-17). Decreased platelet aggregation: ADP 29.7& (30-70), Collagen 14.5% (30-70), AA 14.5% (40-80). Normal response to ristocetin, 88.7% (40-80). Thromboelastography (TEG) examination: hypocoagulable.

CaseHPOFreeText: Cutaneous bleeding, Postpartum bleeding, Blood accumulation in the uterine cavity, Bleeding in ovaries, Vaginal bleeding during pregnancy,

CaseNotHPOs: HP:0011875, Abnormal platelet morphology. HP:0011873, Abnormal platelet count.

ProteinExpression: Protein structure model: destroyed local beta folding structure and molecular changes to structure of GPII beta helical region reduces the expression of GP IIb/IIIa. Proband refused further testing (flow cytometry).

Gene: ITGA2B

Variant: c.2822G>A, p. (Trp941Ter)

HGVS: NM_000419.5:c.2822G>A

ClinVar: absent

CAID: CA399791662

gnomAD: 0.00 https://gnomad.broadinstitute.org/variant/chr17-44375017-C-T?dataset=gnomad_r4

PMID: 8111043

Gene: ITGA2B

HGNC: 6138

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

Case2: Patient LeM

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs:

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Platelets lack surface αIIbβ3 expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.1366_1371del V(425)D(426)del and other other variant is stated as "Unknown" in the GT database. See GT database if questions arise, this is where I found the variants

LegacyVariant: N/A

ClinVar: 2898

CAiD: CA8603160

gnomAD: MAF in the European (non-Finnish) population is 0.000008791 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000419.3%3Ac.1366_1371del

Case1: (Patient MK), Female, Pakistani, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967, HP:0000979

(Petechiae, purpura)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Figure 1 shows protein expression by flow cytometry

PlateletAggregation: Absence of platelet aggregation in response to ADP, epinephrine, and collagen but a normal response to ristocetin

CasePreviousTesting: Genomic DNA containing all of the exons of the aIIb and b3 genes and 500 bp of DNA immediately upstream of each transcriptional start site was isolated from the patient and normal controls. Screening for mutations was performed by using single stranded conformation polymorphism analysis. PCR amplification was performed as well.

Gene: ITGB3

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

LegacyVariant: (p.Leu117Trp)

ClinVar: 13567

CAiD: CA123252

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

PMID: 18976939

Gene: ITGA2B

HGNC: 6138

PMID: 19594615

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions an individual with Hairy cell leukemia who presented with bleeding diathesis diagnosed to have acquired GT. There is no mention of ITGA2B/ ITGB3 variants in this individual.

Case1: Male, 14 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type 1

FamilyInfo: Sister is also heterozygous for this mutation but shows no bleeding symptoms

ParentalGenotype: Both parents are heterozygous for this mutation

Note: There is parental consanguinity

CasePresentingHPOs: HP:0000967, HP:0000225, HP:0000421

(Petechiae, ginigival bleeding, epistaxis)

CaseHPOFreeText: Haematoma,

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry analysis revealed 3.8 % platelet surface presentation of the αIIbβ3 complex for patient 1 and αIIb was not detected and β3 was significantly reduced in Western blots. Platelets from GT patients showed less than 5 % relative levels of the integrin subunit IIb and 5–9 % fibrinogen compared to controls.

PlateletAggregation: Article states agonist-induced platelet aggregation and binding of exogenous fibrinogen was pathological, too but does not mention specific agonists used or response to ristocetin

CasePreviousTesting: Molecular genetic analysis was done; however, no other information mentioned. In addition, the global proteome of highlight purified washed platelets was quantified by liquid chromatography-mass spectrometry and targeted MS-methods.

Gene: ITGA2B

Variant: NM_000419.3:c.175del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940266

gnomAD: N/A

PMID: 22394243

Gene: ITGA2B

HGNC: 6138

PMID: 9062952

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

Case18: Patient LB, gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: Child is patient LN, significant other is patient LH

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: NM_000419.3:c.3062T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399787956

gnomAD: N/A

Case14: Patient TN, 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: NM_000419.3:c.3060G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA500261104

gnomAD: N/A

PMID: 15819676

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

PMID: 15748237

Gene: ITGA2B and ITGB3

HGNC: 6138 and 1656

InsufficientEvidence: This article mentions 22 GT patients and variants, which these patients harbor; however, the article does not specify which patient harbors which variants therefore there is insufficient evidence

PMID: 15701721

Gene: ITGB3

HGNC: 6156

PMID: 22065596

Genes: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention probands or variants in ITGA2B or ITGB3; however, there are some experimental assays for consideration

Supplemental Table S1:

Case5: Male, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding from multiple sites

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 8% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399802348

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

PreviouslyPublished: PMID: 16879215

PMID: 12956766

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions GT patients; however, there are no variants presented in ITGA2B and/or ITGB3

PMID: 20081061

Gene: ITGB3

HGNC: 6156