Supplemental Table S1:

Case37: Female, India, age not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mild bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <5% αIIbβ3 expression

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

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

Gene: ITGA2B

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8602772

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

PreviouslyPublished: PMID: 19172520

Supplementary Tables 1 and 2 combined information:

Case11: GT11, Female, 12 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

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

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

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

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

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

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

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

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

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

gnomAD: N/A

Case29: Strasbourg 1

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: Bruising HP:0000978

CaseHPOFreeText: Hematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

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

LegacyVariant: N/A

ClinVar: 13555

CAiD: CA123228

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

PreviouslyPublished: Ref 46, 47

Case1: Female, 5 years old, South East Asian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Information given on paternal grandmother

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

CasePresentingHPOs: HP:0000978, HP:0000421

(Severe bruising, epistaxis)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Gene: ITGA2B

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

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

ClinVar: 381747 and 417951 and 569057

CAiD: CA16608466 and CA8602498 and CA8602901

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

Case#: Green_Malmo_6 (assumed male)

DiseaseAssertion: Severe Hemophillia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C <1%, FIX:Ag: 26-34)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.127C>T (p.Arg43Trp)

LegacyVariant: c.6364C>T (p.Arg-4Trp)

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: 8, male

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: Proband's mother and sister are confirmed carriers of hemophilia

ParentalTesting: Mother was tested and found to be a carrier of hemophilia

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%, FVIII:Ag = 25%, assay discrepancy present (OSA>CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: For exons 1–13 and 15–26, PCR primers were designed for denaturing gradient gel electrophoresis (DGGE) and exon 14 was amplified in four overlapping fragments and subsequently sequenced. VWF:Ag was tested and found to be within normal ranges.

Gene: F8

Variant: NM_000132.3:c.694A>T

LegacyVariant:

ClinVar: No

CAID: CA414919124

gnomAD:

Case#: 001-2046

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.822G>T

LegacyVariant:

ClinVar: No

CAID: CA337337669

gnomAD:

Case#: 084-2004

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1910A>G

LegacyVariant:

ClinVar: No

CAID: CA414909849

gnomAD:

Case#: 071-2024

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.2167G>A

LegacyVariant:

ClinVar: No

CAID: CA255138

gnomAD:

Case#: 066-2001

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.6098T>C

LegacyVariant:

ClinVar: No

CAID: CA414904604

gnomAD:

Case#: 072-2009

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1332A>T

LegacyVariant:

ClinVar: No

CAID: CA414914974

gnomAD:

Case#: 071-2001

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.901C>T

LegacyVariant:

ClinVar: No

CAID: CA414917990

gnomAD:

Case#: 035-2013

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.5275G>A

LegacyVariant:

ClinVar: No

CAID: CA414911087

gnomAD:

Case#: 091-2010

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1475A>G

LegacyVariant:

ClinVar: No

CAID: CA337334224

gnomAD:

Case#: 071-2023

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.2167G>A

LegacyVariant:

ClinVar: No

CAID: CA255138

gnomAD:

Case#: 091-2005

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.5393C>A

LegacyVariant:

ClinVar: No

CAID: CA414909064

gnomAD:

Case#: 020-2054

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1899G>T

LegacyVariant:

ClinVar: No

CAID: CA414910251

gnomAD:

Case#: 060-2004

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.272T>C

LegacyVariant:

ClinVar: No

CAID: CA414920117

gnomAD:

Case#: 020-2063

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.558C>G

LegacyVariant:

ClinVar: No

CAID: CA414919454

gnomAD:

Case#: 001-2025

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.986G>A

LegacyVariant:

ClinVar: No

CAID: CA255089

gnomAD:

Case#: 020-2038

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1834C>T

LegacyVariant:

ClinVar: No

CAID: CA255129

gnomAD:

Case#: 015-2011

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 1% < FVIII:C < 5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1241A>G

LegacyVariant:

ClinVar: No

CAID: CA414915839

gnomAD:

Case#: 086-2006

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%, Inhibitor present

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.1537G>C

LegacyVariant:

ClinVar: No

CAID: CA414912560

gnomAD:

Case#: 001-2041

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 40%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification

Gene: F8

Variant: NM_000132.3:c.2167G>A

LegacyVariant:

ClinVar: No

CAID: CA255138

gnomAD:

Case#: 52HBT167 (Turkish; assumed male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: Not provided

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: Reduced factor IX activity (FIX:C:3.9)

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.83G>A (p.Cys28Tyr)

LegacyVariant: c.112G>A (p.Cys-19Tyr)

ClinVar: Absent/Not Reported

CAID: CA414434483

gnomAD: Absent/Not Reported

Case#: HB_132 (assumed male)

DiseaseAssertion: Mild-Moderate Hemophilia B

FamilyInfo: Not provided

ParentalTesting: Not provided

CasePresentingHPOs: N/A

CasePresentingHPOsFreeText: Mild-Moderate Hemophilia B, Quality parameters given as read depth and strand bias for the mutated positions: 3098/0.51

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.82T>C (p.Cys28Arg)

ClinVar: 10657

CAID: CA255450

gnomAD: Absent/Not Reported

Case#: 71, male, 6 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 4.2%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.5398C>T

LegacyVariant:

ClinVar: 10275

CAID: CA255163

gnomAD:

Case#: 102, male, 17 years old, Chinese

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 65.7%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.6617A>T

LegacyVariant:

ClinVar: No

CAID: CA414906010

gnomAD:

Case#: 32, male, 18 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.362G>A

LegacyVariant:

ClinVar: No

CAID: CA414919924

gnomAD:

Case#: 37, male, 53 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.397T>C

LegacyVariant:

ClinVar: No

CAID: CA414919824

gnomAD:

Case#: 109, male, 29 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%, Inhibitor present

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.6967C>T

LegacyVariant:

ClinVar: 10333

CAID: CA255225

gnomAD:

Case#: 76, male, 30 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.5551T>C

LegacyVariant:

ClinVar: No

CAID: CA414908519

gnomAD:

Case#: 65, male, 13 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 2.1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.2167G>A

LegacyVariant:

ClinVar: 10246

CAID: CA255138

gnomAD:

Case#: 89, male, 36 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: NA

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.6406G>A

LegacyVariant:

ClinVar: No

CAID: CA414899430

gnomAD:

Case#: 30, male, 27 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 4.1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.361G>A

LegacyVariant:

ClinVar: No

CAID: CA414919926

gnomAD:

Case#: 81, male, 19 years old, Chinese

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 7.1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.5707G>A

LegacyVariant:

ClinVar: No

CAID: CA414907751

gnomAD:

Case#: 62, male, 50 years old, Chinese

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 38.5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.2111C>T

LegacyVariant:

ClinVar: No

CAID: CA414908864

gnomAD:

Case#: 46, male, 21 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 2.3%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.1172G>A

LegacyVariant:

ClinVar: 10111

CAID: CA120918

gnomAD:

Case#: 53, male, 21 years old, Chinese

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 15.9%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.1834C>T

LegacyVariant:

ClinVar: 10236

CAID: CA255129

gnomAD:

Case#: 70, male, 16 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 3%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.5398C>T

LegacyVariant:

ClinVar: 10275

CAID: CA255163

gnomAD:

Case#: 31, male, 41 years old, Chinese

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.361G>A

LegacyVariant:

ClinVar: No

CAID: CA414919926

gnomAD:

Case#: 94, male, 8 years old, Chinese

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: Noted Family History

ParentalTesting: Maternity confirmed

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 8.5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.6448G>A

LegacyVariant:

ClinVar: No

CAID: CA414907951

gnomAD:

Case#: 27, male, 30 years old, Chinese

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA

Gene: F8

Variant: NM_000132.3:c.266G>C

LegacyVariant:

ClinVar: No

CAID: CA414920127

gnomAD:

Case#: Guo_Proband_2 (assumed male; Chinese)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity FIX:C:2.1%; FIX:Ag:1.6

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.59T>C (p.Leu20Ser)

ClinVar: Absent

CAID: CA414434363

gnomAD: Absent/Not Reported

Case#: Guo_Proband_3 (assumed male; Chinese)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs:

CaseHPOsFreeText: reduced factor IX activity FIX:C: 2.9%; FIX:Ag: 3.0)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.83G>A (p.Cys28Tyr)

ClinVar: Absent

CAID: CA414434483

gnomAD: Absent/Not Reported

Case#: 10

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FVIII:C 22% (Mild Phenotype), No inhibitors present

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F8

Variant: NM_000132.3:c.1307A>C (p.Gln436Pro)

ClinVar: NA

CAID: CA414915176

gnomAD: Not reported

Case#: 45

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C 5% (Moderate Phenotype)

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F9

Variant: NM_000133.3:c.689G>A (p.Gly230Glu)

ClinVar: NA

CAID: CA414441179

gnomAD: Not reported

Case#: 20

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FVIII:C 18%, Mild Phenotype, No inhibitors present

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F8

Variant: NM_000132.3(F8):c.5123G>A (p.Arg1708His)

ClinVar: 10266 https://www.ncbi.nlm.nih.gov/clinvar/variation/10266/

CAID: CA255154

gnomAD: MAF for Arg1708His in the South Asian population 0.00005507<br> https://gnomad.broadinstitute.org/variant/X-154156942-C-T?dataset=gnomad_r2_1

Case#: 36

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FVIII:C 33/30%, Mild Phenotype, No inhibitors present

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F8

Variant: NM_000132.3:c.6845C>G (p.Ser2282Cys)

ClinVar: NA

CAID: CA414903435

gnomAD: Not reported

Case#: 3

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FVIII:C 18% (Mild Phenotype), No inhibitors present

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F8

Variant: NM_000132.3(F8):c.396A>C (p.Glu132Asp)

ClinVar: 10171 https://www.ncbi.nlm.nih.gov/clinvar/variation/10171/

CAID: CA255060

gnomAD: MAF for Glu132Asp in Other population 0.0003762<br> https://gnomad.broadinstitute.org/variant/X-154221416-T-G?dataset=gnomad_r2_1

Case#: 41

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C 2/2% (Moderate Phenotype)

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F9

Variant: NM_000133.3:c.1291T>G (p.Trp431Gly)

ClinVar: NA

CAID: CA414447127

gnomAD: Not reported

Case#: 44

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C 23% (Mild Phenotype)

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F9

Variant: NM_001313913.1:c.580G>A (p.Asp194Asn)

ClinVar: NA

CAID: CA414441211

gnomAD: Not reported

Case#: 16

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FVIII:C 31% (Mild Phenotype), No inhibitors present

CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing

Gene: F8

Variant: NM_000132.3:c.2043G>A (p.Met681Ile)

ClinVar: NA

CAID: CA414909257

gnomAD: Not reported

Case#: Patient Q (male, 83 y/o, born in South Germany)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Brother died from a life threatening bleeding complication under phenprocoumon therapy

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858, HP:0012233

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 2%), muscle hematoma of the extremities, subcutaneous bleed of the body and lower extremities.

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.110C>T (p.Ala37Val)

ClinVar: Absent

CAID: CA414435437

gnomAD: Allele Frequency (European-non Finnish): 0.00002186

Case#: Pezeshkpoor_Patient_O (male, 36 y/o, from Switzerland)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0002625, HP:0011858

CaseHPOsFreeText: deep vein thrombosis, low FIX:C levels (<1%), prolonged aPTT of 90 seconds, diffuse muscle bleeding

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.109G>A (p.Ala37Thr)

ClinVar: 804089

CAID: CA10529736

gnomAD: Allele Frequency in population where variant was found in the highest (South Asian population): 0.0001128

AdditionalCaseInfo: Sequencing of SERPINC1 revealed a splice site mutation located at c.1154-14G>A

Case#: Pezeshkpoor_Patient_M (male, 58 y/o, from Switzerland)

DiseaseAssertion: Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: spontaneous bleeding symptoms from the blood, the mouth, the tongue, and epiglottis, low FIX:C levels

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.109G>A (p.Ala37Thr)

ClinVar: 804089

CAID: CA10529736

gnomAD: Allele Frequency in population where variant was found in the highest (South Asian population): 0.0001128

Case#: 18

DiseaseAssertion: Hemophilia B, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0011858

CaseHPOFreeText: FIX:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing

Gene: F9

Variant: NM_000133.3:c.1068G>T

LegacyVariant:

ClinVar: No

CAID: CA414445683

gnomAD:

Case#: 25

DiseaseAssertion: Hemophilia B, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0011858

CaseHPOFreeText: FIX:C = 2%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing

Gene: F9

Variant: NM_000133.3:c.1204G>A

LegacyVariant:

ClinVar: No

CAID: CA414446446

gnomAD:

Case#: 12

DiseaseAssertion: Hemophilia B, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0011858

CaseHPOFreeText: FIX:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing

Gene: F9

Variant: NM_000133.3:c.761G>A

LegacyVariant:

ClinVar: No

CAID: CA414443235

gnomAD:

Case#: 5

DiseaseAssertion: Hemophilia B, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0011858

CaseHPOFreeText: FIX:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing

Gene: F9

Variant: NM_000133.3:c.305G>T

LegacyVariant:

ClinVar: No

CAID: CA414437422

gnomAD:

Case#: 17

DiseaseAssertion: Hemophilia B, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0011858

CaseHPOFreeText: FIX:C = 3%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing

Gene: F9

Variant: NM_000133.3:c.1025C>T

LegacyVariant:

ClinVar: No

CAID: CA255381

gnomAD:

Case#: Meireles_Proband_2 (assumed male)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: None

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Trp)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Meireles_Proband_4 (assumed male)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: None

Gene: F9

Variant: NM_000133.4:c.127C>T (p.Arg43Trp)

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Family HB55

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>T (p.Arg43Leu)

ClinVar: 993549

CAID: CA414435545

gnomAD: Absent/Not Reported

Case#: A2, A3

DiseaseAssertion: Hemophilia A, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C = 4, FVIII:AG = 35, assay discrepancy present (OSA>CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers

Gene: F8

Variant: NM_000132.4:c.881C>T

LegacyVariant:

ClinVar: No

CAID: CA255077

gnomAD:

Case#: B75

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C Chr = 9, FVIII:AG = 10, inverse assay discrepancy present (OSA<CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers

Gene: F8

Variant: NM_000132.4:c.5323T>G

LegacyVariant:

ClinVar: No

CAID: CA255159

gnomAD:

Case#: B76

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C Chr = 7, FVIII:AG = 10, inverse assay discrepancy present (OSA<CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers

Gene: F8

Variant: NM_000132.4:c.5398C>G

LegacyVariant:

ClinVar: No

CAID: CA255164

gnomAD:

Case#: B45 - B72

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: FVIII:C Chr = 9, FVIII:AG = 16, inverse assay discrepancy present (OSA<CSA)

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers

Gene: F8

Variant: NM_000132.4:c.5096A>T

LegacyVariant:

ClinVar: No

CAID: CA255022

gnomAD:

Case#: 15, Spanish

DiseaseAssertion: Hemophilia A

FamilyInfo: Sporadic

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NA

ClinVar: NA

gnomAD: NA

Case#: 27

DiseaseAssertion: Hemophilia A

FamilyInfo: Positive

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NM_000132.3:c.6317A>C (p.Gln2087Pro)

ClinVar: NA

CAID: CA414900070

gnomAD: Not reported

Case#: 22

DiseaseAssertion: Hemophilia A

FamilyInfo: Sporadic

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NM_000132.3:c.1706C>G (p.Pro550Arg)

ClinVar: NA

CAID: CA414911701

gnomAD: Not reported

Case#: 26

DiseaseAssertion: Hemophilia A

FamilyInfo: Positive

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Mild

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NM_000132.3(F8):c.6301C>G (p.His2101Asp)

ClinVar: 804137 https://www.ncbi.nlm.nih.gov/clinvar/variation/804137/

CAID: CA414900220

gnomAD: Not reported

Case#: 14, Spanish

DiseaseAssertion: Hemophilia A

FamilyInfo: Sporadic

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NM_000132.3:c.584T>C (p.Leu195Pro)

ClinVar: NA

CAID: CA414919399

gnomAD: Not reported

Case#: 25

DiseaseAssertion: Hemophilia A

FamilyInfo: Sporadic

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Moderate

CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit

Gene: F8

Variant: NM_000132.3:c.5286T>A (p.Phe1743Leu)

ClinVar: NA

CAID: CA414910973

gnomAD: Not reported

Case#: S30, Iranian

DiseaseAssertion: Hemophilia A, mild

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125

CaseHPOFreeText: 5% < FVIII:C < 30%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed

Gene: F8

Variant: NM_000132.3:c.2090T>C

LegacyVariant:

ClinVar: No

CAID: CA414909005

gnomAD:

Case#: S21, Iranian

DiseaseAssertion: Hemophilia A, severe

FamilyInfo: Family history of HA

ParentalTesting: NA

CasePresentingHPOs: HP:0003125, HP:0005261

CaseHPOFreeText: FVIII:C < 1%, Inhibitor present

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed

Gene: F8

Variant: NM_000132.3:c.6213A>T

LegacyVariant:

ClinVar: No

CAID: CA414903164

gnomAD:

Case#: Gostout_Proband_189 (assumed male, Asian (from India))

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 3%)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.127C>T (p.Arg43Trp)

LegacyVariant: c.6364C>T (p.Arg-4Trp)

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: UQU-HB4, Male, 6-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe, PTT 60.1

CasePreviousTesting: Screened for all factor IX exons by capillary sequencing

Gene: F9

Variant: NM_000133.3(F9):c.1025C>T (p.Thr342Met)

ClinVar: 10607 https://www.ncbi.nlm.nih.gov/clinvar/variation/10607/

CAID: CA255381

gnomAD: Not reported

Case#: UQU-HB2, Male, 2-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe, PTT 74.5, Disabled right knee

CasePreviousTesting: Screened for all factor IX exons by capillary sequencing

Gene: F9

Variant: NM_001313913.1:c.580G>A (p.Asp194Asn)

ClinVar: NA

CAID: CA414441211

gnomAD: Not reported

Case#: UQU-HA36, Male, 1-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia A

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0001892 (Abnormal bleeding)

CaseHPOFreeText: Mild, FVIII: 1 to <5% (moderate HA) based on text

CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons

Gene: F8

Variant: NM_000132.3:c.99G>T (p.Trp33Cys)

ClinVar: NA

CAID: CA414920529

gnomAD: Not reported

Case#: 8

DiseaseAssertion: Hemophilia B, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C = 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing

Gene: F9

Variant: NM_000133.3:c.349T>C

LegacyVariant:

ClinVar: No

CAID: CA414437669

gnomAD:

Case#: 16

DiseaseAssertion: Hemophilia B, moderate

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C = 1.5%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing

Gene: F9

Variant: NM_000133.3:c.427C>G

LegacyVariant:

ClinVar: No

CAID: CA414438921

gnomAD:

Case#: 11

DiseaseAssertion: Hemophilia B, severe

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C < 1%

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing

Gene: F9

Variant: NM_000133.3:c.676C>T

LegacyVariant:

ClinVar: No

CAID: CA255350

gnomAD:

Case#: HB15 (assumed male, Tunisian)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX: <1)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Patient B (assumed male)

DiseaseAssertion: Moderate, Sporadic Hemophilia B

FamilyInfo: Patient B is deceased and only a DNA sample was available; his two sisters and mother are carriers

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: None

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

LegacyVariant: c.6365 G>A (p.Arg-4Gln)

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Ivaskevicius_Proband_LT65 (assumed male, Lithuanian)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 0)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.127C>T (p.Arg43Trp)

LegacyVariant: c.6364C>T (p.Arg-4Trp)

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: N/A

CaseHPOsFreeText: N/A

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.71T>C (p.Leu24Pro)

ClinVar: Absent

CAID: CA414434410

gnomAD: Absent/NotReported

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: N/A

CaseHPOsFreeText: N/A

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.59T>C (p.Leu20Ser)

ClinVar: Absent

CAID: CA414434363

gnomAD: Absent/NotReported

Case#: Li_Proband_1 (male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: Not provided

ParentalTesting: Not provided

CasePresentingHPOs: N/A

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.82T>C (p.Cys28Arg)

ClinVar: 10657

CAID: CA255450

gnomAD: Absent/Not Reported

Case#: Patient A (assumed male)

DiseaseAssertion: Severe (sporadic) Hemophilia B

FamilyInfo: Variant also localized in affected brother, mother (Native American descent) is deceased but maternal grandmother and two maternal aunts screened negative, researchers believe this de novo mutation originated during either grandparent’s gametogenesis.

ParentalTesting: Mother deceased, no mention of father

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: FIX Clotting Activity (U/dl): < 1, Antigen Level (U/dl): < 1

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.50T>A (p.Ile17Asn)

LegacyVariant: c.79T>A (p.Ile-30Asn)

ClinVar: Absent

CAID: CA414434315

gnomAD: Absent/Not Reported

Case#: Liu_Proband_56/439/440/486/830 (assumed male; Chinese)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.128G>A (p.Arg43Gln)

ClinVar: Absent

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Liu_Proband_438 (assumed male; Chinese)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.127C>T (p.Arg43Trp)

ClinVar: Absent

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Salviato_Proband_2164 (male, Chinese)

DiseaseAssertion: Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.83G>A (p.Cys28Tyr)

ClinVar: Absent

CAID: CA414434483

gnomAD: Absent/Not Reported