Case#: Saad_Probands 83-85 (assumed male; from UK)

DiseaseAssertion: Saad_Proband 83: Severe Hemophilia B ; Saad_Probands 84-85: Moderate Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Proband 83: FIX:C: <1, Proband 84: FIX:C 1.6, Proband 85: FIX:C: 4)

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Saad_Probands 86-92 (assumed male; from UK)

DiseaseAssertion: Saad_Probands 86-87: no disease assertion made ; Saad_Probands 88, 90, 91: Moderate Hemophilia B ; Saad_Probands 89, 92: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Proband_88 FIX:C:1 ; FIX:Ag:48, Proband_ 89 FIX:C: <1, Proband_90: FIX:C: 1 ; FIX:Ag:45, Proband_91: FIX:C: 2, Proband_92: FIX:C:<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#: Variant #24 (no specific case; 5 patients and 5 families have variant)

DiseaseAssertion: Severe (2), Moderate (1), Mild (2)

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: Absent/Not Reported

CAID: CA414435539

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.110C>A (p.Ala37Asp)

ClinVar: Absent

CAID: CA414435430

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.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#: 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.68T>C (p.Leu23Pro)

ClinVar: Absent

CAID: CA414434403

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.112A>C (p.Asn38His)

ClinVar: Absent

CAID: CA414435439

gnomAD: Absent/NotReported

Case#: N/A

DiseaseAssertion: Mild 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.62G>T ((p.Gly21Val)

ClinVar: Absent

CAID: CA414434385

gnomAD: Absent/NotReported

Case#: Nawaz_Proband_H (karachi) (Pakistan resident)14 y/o)

DiseaseAssertion: Hemophilia B (no severity assertion made)

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: N/A

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#: Ghanem_Caen (assumed male, from Caen)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 2 ; FIX:Ag: 52

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#: Ghanem_Paris 2 (assumed male, from Paris) & Ghanem_ Caen 2 (assumed male, from Caen)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Paris 2: FIX:C: <1, FIX:Ag: 28, Caen 2: FIX:C: <1

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 811505

CAID: CA414435537

gnomAD: Highest AF (South Asian population): 0.0004904

Case#: Cases 1464

DiseaseAssertion: Familial Severe Hemophilia B

FamilyInfo: In 16 cases, the family pedigree showed more than one affected individual (familial cases) and 12 cases were sporadic. In 17 cases, familial data was not available.

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

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

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Cases 1157, 1125, 1382, and 1434

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: In 16 cases, the family pedigree showed more than one affected individual (familial cases) and 12 cases were sporadic. In 17 cases, familial data was not available.

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Case 1157 FIX:C: <1; FIX:Ag: 38) (Case 1125 FIX:C: <1; FIX:Ag: n/a (Case 1382 FIX:C: <1; FIX:Ag: 1) Case 1434 FIX:C <1; FIX:Ag: n/a)

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#: Wulff_Proband_2252 and Wulff_Proband_2270

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

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#: Attali_LY23 (assumed male, from France)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1 ; FIX:Ag: 44)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Attali_LY04 (assumed male, from France)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: 3 ; FIX:Ag: 41)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Wulff_Proband_031 & Wulff_Proband_048

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Proband_031: FIX:C: <1 FIX:Ag: 48 ; Proband_048 FIX:C <1 FIX:Ag: 52

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#: Family HB130

DiseaseAssertion: Mild Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C : 20%)

CaseNotHPOs: N/A

CasePreviousTesting:

Gene: F9

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

LegacyVariant: c.111T>C (p.Cys-19Arg)

ClinVar: 10657

CAID: CA255450

gnomAD: Absent/Not Reported

Case#: Miller_Proband 1 (male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

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#: Miller_Proband 2 (male)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Oldenburg_Patient_A and Oldenburg_Patient_C

DiseaseAssertion: Mild Hemophilia B (exacerbated due to phenprocoumon administration)

FamilyInfo: The parents of patients A and C emigrated from the same region in North-Eastern Europe (North Poland)

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity, severe bleeding at each oral anticoagulation with phenprocoumon occurrence, bleeding in muscles of the upper leg

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: Absent

CAID: CA414435437

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

Case#: HB-KHF-04 (Male, Korean)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Among the 33 patients, 13 had a family history (39%), while the rest of the patients did not (sporadic, 61%). 27 patients (82%) had the severe form of the disease, while 6 patients (18%) had the moderate form

ParentalTesting: N/A

CasePresentingHPOs: HP:0003645, HP:0011858

CaseHPOsFreeText: Prolonged partial thromboplastin time, reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: aPTT and one-stage clotting assay at labs where patients were ascertained: FIX-deficient plasma (STA®-Deficient IX; Diagnostica Stago, Asnieres-sur-Seine, France; reference range, 60–150%) at Samsung Medical Center or HemosIL™ (Instrumentation Laboratory, Milan, Italy; reference range, 50–145%) at the Korea Hemophilia Foundation.

Gene: F9

Variant: NM_000133.4:c.68T>C (p.Leu23Pro)

ClinVar: Absent

CAID: CA414434403

gnomAD: Absent/Not Reported

Case#: HB-KHF-04 (Male, Korean)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Among the 33 patients, 13 had a family history (39%), while the rest of the patients did not (sporadic, 61%). 27 patients (82%) had the severe form of the disease, while 6 patients (18%) had the moderate form

ParentalTesting: N/A

CasePresentingHPOs: HP:0003645, HP:0011858

CaseHPOsFreeText: Prolonged partial thromboplastin time, reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: aPTT and one-stage clotting assay at labs where patients were ascertained: FIX-deficient plasma (STA®-Deficient IX; Diagnostica Stago, Asnieres-sur-Seine, France; reference range, 60–150%) at Samsung Medical Center or HemosIL™ (Instrumentation Laboratory, Milan, Italy; reference range, 50–145%) at the Korea Hemophilia Foundation.

Gene: F9

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

ClinVar: Absent

CAID: CA414434410

gnomAD: Absent/Not Reported

Case#: HB-KHF-25 (Male, Korean)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Among the 33 patients, 13 had a family history (39%), while the rest of the patients did not (sporadic, 61%). 27 patients (82%) had the severe form of the disease, while 6 patients (18%) had the moderate form

ParentalTesting: N/A

CasePresentingHPOs: HP:0003645, HP:0011858

CaseHPOsFreeText: Prolonged partial thromboplastin time, reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: aPTT and one-stage clotting assay at labs where patients were ascertained: FIX-deficient plasma (STA®-Deficient IX; Diagnostica Stago, Asnieres-sur-Seine, France; reference range, 60–150%) at Samsung Medical Center or HemosIL™ (Instrumentation Laboratory, Milan, Italy; reference range, 50–145%) at the Korea Hemophilia Foundation.

Gene: F9

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

ClinVar: 993549

CAID: CA414435545

gnomAD: Absent/Not Reported

Case#: Tamura_Case (male, 49 y/o)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: No family history of stroke, thrombosis or bleeding episodes

ParentalTesting: N/A

CasePresentingHPOs: HP:0012233, HP:0011858

CaseHPOsFreeText: cerebral infarction, prolonged APTT (58.4 s), elevated diluted Russell viper venom time ratio (2.68), and anti-β2 glycoprotein I antibody (9.7 U/mL) and anticardiolipin antibody IgG (39 U/mL), antiphospholipid antibody syndrome (APS), intramuscular hemorrhage, reduced factor IX activity (<0.5%)

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#: P3 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: Father was tested; has mild HA

CasePresentingHPOs: HP:0003125, HP:0001928

CaseHPOFreeText: Low FVIII levels (significant decrease in FVIII:C (48.4% ± 6.1, P < 0.01) and FVIII:Ag (36.6% ± 2.7, P < 0.01)), abnormal blood coagulation

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.1562C>T

CAID: CA414912242

gnomAD: Absent/Not Reported

CaseInfo: P2 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0003125, HP:0004846, HP:0001892

CaseHPOFreeText: Low FVIII levels (undetectable FVIII:C levels and significant decrease in FVIII:Ag levels: 1.7% ± 1.1), prolonged bleeding after surgery, mild bleeding tendency

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection were also performed.

Gene: F8

Variant: NM_000132.3:c.943del

CAID: CAID:CA255085

gnomAD: Absent/Not Reported

Case#: P1 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0003125, HP:0004846, HP:0001892

CaseHPOFreeText: Low FVIII levels (significant decrease in FVIII:C 1.4% ± 0.2 and FVIII:Ag levels 3.9% ± 0.2), prolonged bleeding after surgery, mild bleeding tendency

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.320T>A

CAID: CA414920017

gnomAD: Absent/Not Reported

Case Info: P6 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0003125, HP:0001928, HP:0001892

CaseHPOFreeText: Low FVIII levels (in vitro results were similar to the WT control and led to a normal specific activity (82.7% ± 9.0)), abnormal blood coagulation, mild bleeding tendency

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.6095T>C

CAID: CA414904631

gnomAD: Absent/Not Reported

Case#: P5 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: Investigation found that large gene defect was not found in the patient P5's mother and grandmother

CasePresentingHPOs: HP:0003125, HP:0001928, HP:0001892

CaseHPOFreeText: Low FVIII levels (FVIII:C levels were significantly decreased compared to the WT (13.4% ± 0.8, P < 0.01); FVIII:Ag levels were normal both in the conditioned media and cell lysate (respectively 90.7% ± 6.3 and 109.0% ± 9.5)), abnormal blood coagulation, mild bleeding tendency, haematoma

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.2044G>C

CAID: CA414909252

gnomAD: Absent/Not Reported

Case#: P4 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0003125, HP:0001928

CaseHPOFreeText: Low FVIII levels (FVIII:Ag showed a moderate reduction (29.8% ± 1.7, p < 0.01) compared to the WT; FVIII:C undetectable), abnormal blood coagulation

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.1730C>A

CAID: CA414911649

gnomAD: Absent/Not Reported

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#: Green_London_3 & Green_London_4 (assumed male)

DiseaseAssertion: Severe Hemophillia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (London 3: FIX:C:1, FIX:Ag: 48) (London 4: FIX:C:1, FIX:Ag: 45)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

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#: 27HBT98 (Turkish; assumed male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: Not provided

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: Reduced factor IX activity (FIX:C: 2)

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#: 37HBT150 (Turkish; assumed male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: Not provided

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: Reduced factor IX activity (FIX:C: 1.3)

CasePreviousTesting: N/A

Gene: F9

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

LegacyVariant: c.6365 G>T (p.Arg-4Leu)

ClinVar: 993549

CAID: CA414435545

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#: HB_140 (assumed male)

DiseaseAssertion: Moderate-Severe Hemophilia B

FamilyInfo: Not provided

ParentalTesting: Not provided

CasePresentingHPOs: N/A

CasePresentingHPOsFreeText: Moderate-Severe Hemophilia B, Quality parameters given as read depth and strand bias for the mutated positions: 1575/0.48

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#: 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#: Guo_Proband_5 (assumed male; Chinese)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity FIX:C: <1 %; FIX:Ag: 35)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.138G>C (p.Arg46Ser)

ClinVar: Absent

CAID: CA414435594

gnomAD: Absent/Not Reported

Case#: Guo_Family 2_Proband 1 (Chinese, assumed male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: FIX:Ag: 1.6%, FIX:C: 2.1%

CaseNotHPOs: 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#: 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#: Pezeshkpoor_Patient_L (male,. 70 y/o, from Switzerland)

DiseaseAssertion: Hemophilia B

FamilyInfo: Mutation was identified in two brothers and six female relatives

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: bleeding episodes during VKA therapy, 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#: Pezeshkpoor_Patient_P (male, 68 y/o, from Switzerland)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: diffuse subcutaneous bleeding, low FIX:C levels (3%), international normalized ratio (INR) of 3.3, a prolonged aPTT of 88 s, reduced vitamin K-dependent coagulation factors

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#: Patient R (male, 83 y/o)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858, HP:0012233

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 2.4%), extensive subcutaneous bleeding

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_N (male, 68 y/o, from Switzerland)

DiseaseAssertion: Hemophilia B

FamilyInfo: The daughter of the patient has the mutation, while the brother of the patient does not.

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: mechanical aoritc valve replacement, 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#: 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#: Meireles_Proband_3 (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>T (p.Arg43Leu)

ClinVar: 993549

CAID: CA414435545

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#: 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#: Patient E (assumed male)

DiseaseAssertion: Severe, Familial Hemophilia B

FamilyInfo: Mothers were heterozygous, but patient E’s sister and aunt were non-carriers (homozygous for the cleavage)

ParentalTesting: Mothers were heterozygous, but patient E’s sister and aunt were non-carriers (homozygous for the cleavage)

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1; FIX:Ag:37/38)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.135G>T (p.Lys45Asn)

ClinVar: Absent/Not Reported

CAID: CA414435576

gnomAD: Absent/Not Reported

Case#: Patient D (assumed male)

DiseaseAssertion: Severe, Sporadic Hemophilia B

FamilyInfo: Patient D's mother is heterozygous and she has had a second, affected son. the maternal grandmother's DNA was also heterozygous

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1; FIX:Ag:41)

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#: Patient A (assumed male)

DiseaseAssertion: Moderate, Familial Hemophilia B

FamilyInfo: Mother and two sisters were heterozygous for the CG to CA transition; One sister’s prenatal sample was hemizygous for absence of cleavage indicating an affected male, confirmed after birth.

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 2 FIX:Ag: 40)

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#: Patient C (assumed male)

DiseaseAssertion: Severe, Sporadic Hemophilia B

FamilyInfo: Patient C's mother and two sisters were also heterozygous; and the third sister was homozygous for cleavage and is a non-carrier

ParentalTesting: Mother was heterozygous for the variant

CasePresentingHPOs: HP:0011858

CasePresentingHPOsFreeText: reduced factor IX activity (FIX:C: <1; FIX:Ag:65)

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#: 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#: Liu_Proband_316 (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.82T>G (p.Cys28Gly)

ClinVar: Absent

CAID: CA414434482

gnomAD: Absent/Not Reported

Case#: Liu_Proband_322 (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.59T>C (p.Leu20Ser)

ClinVar: Absent

CAID: CA414434363

gnomAD: Absent/Not Reported

Case#: Gostout_Proband_280 (assumed male, Asian (from Japan))

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: 1.8%)

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#: 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

Case#: Salviato_Proband_1164 (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.59T>C (p.Leu20Ser)

ClinVar: Absent

CAID: CA414434363

gnomAD: Absent/Not Reported

Case#: Salle_Proband_J-C L (male, 23 y/o, white)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: family history is negative for any haemostatic disorder

ParentalTesting: family history is negative for any haemostatic disorder

CasePresentingHPOs: HP:0011858, HP:0012233, HP:0000421

CaseHPOsFreeText: reduced factor IX activity (FIX:C: <0.01 % FIX:Ag: 0.46), muscular haematoma, haemarthrosis, nose bleeding

CaseNotHPOs: N/A

CasePreviousTesting: None

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Nummi_Proband_6 (assumed male)

DiseaseAssertion: Moderate Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0001929 (FIX baseline clotting activity: 1

CaseHPOsFreeText: reduced factor IX activity

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#: Oldenburg Cases A, B and C (A: 66 y/o, B: 38 y/o, C: 30 y/o (all in Germany))

DiseaseAssertion: Mild Hemophilia B

FamilyInfo: No bleeding tendency noted in any of these patients family history

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: severe bleeding at each occasion of oral anticoagulation with phenoprocoumon, bleeding was located in the muscles of the upper leg (patients A and C) and scrotum, left calf and thigh musles (patient B), reduced factor IX levels

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

LegacyVariant: p.Ala-10Thr

ClinVar: 804089

CAID: CA10529736

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

AdditionalCaseInfo: all patients were unrelated up to the third generation. However, the parents of patients A and C emigrated from the same region in North-Eastern Europe (North Poland)

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0001929

CasePresentingHPOsFreeText: reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.84T>G (p.Cys28Trp)

ClinVar: Absent

CAID: CA414434487

gnomAD: Absent/Not Reported

Case#: N/A

DiseaseAssertion: Mild Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0001929

CasePresentingHPOsFreeText: reduced factor IX activity

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.62G>T (p.Gly21Val)

ClinVar: Absent

CAID: CA414434385

gnomAD: Absent/Not Reported

Case#: Weinmann_Family 9248

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: 16 of the families were from the Pacific Northwest, 4 from Colorado, and 6 were referred from elsewhere in the United States

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1%, FIX:Ag: 37)

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

LegacyVariant: c.6364C>T

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_15 (male, Italian)

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: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_13 (male, Italian)

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.110C>A (p.Ala37Asp)

ClinVar: Absent

CAID: CA414435430

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_16 (Italian)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant:NM_000133.4:c.135G>C (p.Lys45Asn)

ClinVar: Absent

CAID: CA414435574

gnomAD: Absent/Not Reported

Case#: HBF12 (North Indian origin)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: For each patient at least two first or second degree relatives were also analyzed. In every case the mother of the patient was analyzed to establish the presence of the mutation in the heterozygous state.

ParentalTesting: Mother

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_7 (Italian)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

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

ClinVar: Absent

CAID: CA414434483

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_6 (Italian)

DiseaseAssertion: Mild Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

LegacyVariant: c.11T>C (p.Cys-19Arg )

ClinVar: 10657

CAID: CA255450

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_4 (male, Italian)

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.59T>C (p.Leu20Ser)

ClinVar: Absent

CAID: CA414434363

gnomAD: Absent/Not Reported

Case#: Belvini_Proband_14 (male, Italian)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

LegacyVariant:

ClinVar: 811505

CAID: CA414435537

gnomAD: Absent/Not Reported

Case#: Riegelsberg (male)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Mother carries only the G-to-A transition (age at conception: 30 y/o). Origin of variant cannot be proved, since maternal grandparents were deceased at time of report.

ParentalTesting: Mother carries only the G-to-A transition, father shows to not be affected (figure 1)

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: FIX Coagulant %: < 1, FIX Antigen %: < 1

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.8G>A (p.Arg3His)

LegacyVariant: c.37G>A

ClinVar: 695909

CAID: CA10529706

gnomAD: Filtering AF: 0.0002304 (no homozygotes)

Case#: Taipei_1 & Taipei_2 (assumed male; Chinese)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Mothers of both families were found to be carriers as well as several other females in the family

ParentalTesting: Mothers were carriers

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (Patient 1: FIX:C: <1% FIX:Ag: 38 ; Patient 2: FIX:C: <1% ; FIX:Ag: 55)

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#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: Not provided

ParentalTesting: Not provided

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.82T>G (p.Cys28Gly)

ClinVar: Absent

CAID: CA414434482

Case#: N/A

DiseaseAssertion: Moderate/Mild Hemophilia B

FamilyInfo: Not provided

ParentalTesting: Not provided

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: 10657

CAID: CA255450

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0001929

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.138G>T (p.Arg46Ser)

ClinVar: Absent

CAID: CA414435596

gnomAD: Absent/Not Reported

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0001929

CaseHPOsFreeText: reduced factor IX activity

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

Variant: NM_000133.4:c.135G>T (p.Lys45Asn)

ClinVar: Absent

CAID: CA414435576

gnomAD: Absent/Not Reported

Case#: N/A

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: None

CasePresentingHPOs: HP:0001929

CaseHPOsFreeText: reduced factor IX activity

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