242 Matching Annotations
  1. Oct 2026
    1. mutations

      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

    2. mutations

      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

    1. The final list of mutations is provided in Supplementary Table S1.

      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

    2. The final list of mutations is provided in Supplementary Table S1.

      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

    3. The final list of mutations is provided in Supplementary Table S1.

      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

    4. The final list of mutations is provided in Supplementary Table S1.

      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

    5. The final list of mutations is provided in Supplementary Table S1.

      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

    6. The final list of mutations is provided in Supplementary Table S1.

      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

    1. mutations

      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

    2. mutations

      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

    1. mutation

      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

    2. mutation

      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

    1. mutation

      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

    2. mutation

      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

    1. Cysteine 19--arginine (in patient HB13O) alters thesignal peptide. The factor IX activity (20%) in thepatient record suggests mild disease

      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

    1. Table S3. F9 mutations.

      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

    2. Table S3. F9 mutations

      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

    1. Ala-10 residue (Ala[GCC) to Val[GCT]

      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

    1. Leu-23Pro

      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

    2. (Leu24Pro)

      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

    3. Arg-4Leu (Arg43Leu)

      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

    1. p.Ala37Thr

      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

    1. The p.Pro521Leu substitution (patient P3)

      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

    2. p.Ala315dup (patient P2)

      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

    3. Both p.Leu107His substitution (patient P1)

      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

    4. The p.Leu2032Pro

      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

    5. For p.Val682Leu,

      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

    6. For p.Ser577Tyr mutation (patient P4)

      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

    1. mutation

      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

    2. mutation

      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

    1. Cys-19Tyr

      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

    2. Arg-4Gln

      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

    3. Arg-4Leu

      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

    1. HB_132

      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

    2. HB_140

      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

    1. c.59T>C p.Leu20Ser

      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

    2. c.83G>A p.Cys28Tyr

      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

    3. c.138G>C p.Arg46Ser

      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

    4. 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

    1. Val37 mutation.

      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

    2. Thr37 mutation

      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

    3. Thr37 mutation

      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

    4. Thr37

      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

    5. Thr37 mutation

      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

    6. Val37 mutation.

      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

    7. Thr37

      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

    1. c.128G>A

      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

    2. c.127C>T

      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

    3. c.128G>T

      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

    1. 6365

      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

    2. (6372)

      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

    3. Arg- > Gln

      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

    4. 6365

      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

    5. Arg- > Gln

      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

    1. 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

    1. 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

    2. 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

    3. 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

    4. 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

    1. mutations in the factor IX gene resulting in hemophilia B.

      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

    1. c.83G>A

      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

    2. c.59T>C

      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

    1. mutant factor IX

      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

    1. 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)

    1. p.Cys28Trp

      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

    2. .Gly21Val)

      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

    1. Mutations

      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

    1. identify the causative mutation

      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

    2. identify the causative mutation

      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

    3. mutation

      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

    4. ion of a causative mutation

      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

    5. identify the causative mutation

      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

    6. identify the causative mutation

      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

    7. identify the causative mutation

      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

    8. identify the causative mutation

      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

    1. 37, G-IA

      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)

    1. genetic defects

      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

    1. p.Cys28Gly

      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

    2. p.Cys28Arg

      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

    1. R46S

      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

    2. K45N

      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

    3. C28Y

      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

    4. I17N

      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.50T>A (p.Ile17Asn)

      ClinVar: Absent

      CAID: CA414434315

      gnomAD: Absent/Not Reported

    1. Case#: Calgary 4

      DiseaseAssertion: Hemophilia B

      FamilyInfo: 9 carrier females, 3 affected males, 1 female obligate carrier

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0001929

      CaseHPOsFreeText: reduced factor IX activity

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      Gene: F9

      Variant: c.19A>T (p.Ile7Phe)

      LegacyVariant: c.48A>T (p.Ile-40Phe)

      ClinVar: Absent

      CAID: CA10529708

      gnomAD: Filtering AF: 0.0007752 (no homozygotes)

      Variant: NM_000133.3:c.1150C>T (p.Arg384Ter)

      LegacyVariant: c.31133C>T (p.Arg338Ter)

      ClinVar: Absent

      CAID: CA255399

      gnomAD: Absent/Not Reported

    1. Factor IX San Dima

      Case#: Factor IX San Dimas Case

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: None

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (FIX:Ag 98%; FIX:C: <0.01)

      CaseNotHPOs: N/A

      CasePreviousTesting: DNA Seq analysis of the Factor IX gene (FIX:Ag 98%; FIX:C: <0.01)

      Gene: F9

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

      LegacyVariant: p.Arg-4Gln

      ClinVar: 810864

      CAID: CA414435539

      gnomAD: Absent/Not Reported

    1. Case#: IG2 (Italian, assumed male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1%, FIX:Ag: 15-53)

      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

    2. Case#: IG13 (Italian, assumed male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: HP:0011858

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

      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

    3. Case#: IG38 (Italian, assumed male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1%, FIX:Ag: 20)

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

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

      LegacyVariant: c.16364C>T (p.Arg-4Trp)

      ClinVar: 811505

      CAID: CA414435537

      gnomAD: Absent/Not Reported

    1. Case#: 043 (GB); Polish origin

      DiseaseAssertion: Moderate Hemophilia B

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: HP:0011858

      CasePresentingHPOsFreeText: FIX:C : 4; FIX:Ag : 4

      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

    2. Case#: 014 (AD); Polish origin

      DiseaseAssertion: Moderate Hemophilia B

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: HP:0011858

      CasePresentingHPOsFreeText: FIX:C : 2; FIX:Ag : 65

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

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

      ClinVar: Absent/Not Reported

      CAID: CA414435596

      gnomAD: Absent/Not Reported

    1. Table 1

      Case#: N/A

      DiseaseAssertion: Severe/Moderate Hemophilia B

      FamilyInfo: N/A

      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

    2. Table 1

      Case#: N/A

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: N/A

      ParentalTesting: None

      CasePresentingHPOs: HP:0001929

      CaseHPOsFreeText: reduced factor IX activity

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

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

      ClinVar: Absent

      CAID: CA414434487

      gnomAD: Absent/Not Reported

    1. Click here for additional data file.

      Case#: N/A

      DiseaseAssertion: Hemophilia B (severity not specified)

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: Not provided

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

      Variant: NM_000133.4:c.86C>T (p.Thr29Ile)

      ClinVar: Absent

      CAID: CA414434494

      gnomAD: Absent/NotReported

    2. Click here for additional data file

      Case#: N/A

      DiseaseAssertion: Hemophilia B (severity not specified)

      FamilyInfo: Not provided

      ParentalTesting: Not provided

      CasePresentingHPOs: Not provided

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

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

      ClinVar: Absent

      CAID: CA414434403

      gnomAD: Absent/NotReported

    1. mutation

      Case#: Heit_Proband_HB541 (assumed male, AmerIndian from Peru)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: N/A

      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

    2. mutation

      Case#: Heit_Proband_HB541 (assumed male, AmerIndian from Peru)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: N/A

      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.137G>C (p.Arg46Thr)

      LegacyVariant: c.6374 G>C (p.Arg-1Thr)

      ClinVar: Absent/Not Reported

      CAID: CA414435590

      gnomAD: Absent/Not Reported

    3. mutation

      Case#: Heit_Proband_HB535 (assumed male, AmerIndian from Peru)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: N/A

      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.127C>T (p.Arg43Trp)

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

      ClinVar: 811505

      CAID: CA414435537

      gnomAD: Absent/Not Reported

    1. mutation

      Case#: HB189 (assumed male, Hawaiian)

      DiseaseAssertion: No disease assertion made

      FamilyInfo: Of the 30 families, germline or so- matic origins were found in 9 mothers, 5 maternal grandmothers, and 16 maternal grandfathers. For the 29 incomplete families, origins were found in 14 mothers, 5 maternal grandmothers, and 10 maternal grandfathers. Comparing the two family types shows no significant difference (P=0.29), suggesting that no major bias occurs in the analyses because of the inclusion of incomplete families

      ParentalTesting: N/A

      CasePresentingHPOs: N/A

      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

    2. mutation

      Case#: HB348 (assumed male, Caucasian, 28 y/o)

      DiseaseAssertion: No disease assertion made

      FamilyInfo: Of the 30 families, germline or so- matic origins were found in 9 mothers, 5 maternal grandmothers, and 16 maternal grandfathers. For the 29 incomplete families, origins were found in 14 mothers, 5 maternal grandmothers, and 10 maternal grandfathers. Comparing the two family types shows no significant difference (P=0.29), suggesting that no major bias occurs in the analyses because of the inclusion of incomplete families

      ParentalTesting: N/A

      CasePresentingHPOs: N/A

      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

    1. ile 40-phe

      Case: E91M

      DiseaseAssertion: Hemophilia B

      FamilyInfo: Family E91M

      ParentalTesting: Not available

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Factor IX Coagulant: 30

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

      Variant: NM_000133.4:c.19A>T

      LegacyVariant: c.48A>T (p.Ile7Phe)

      ClinVar: 367997

      CAID: CA10529708

      gnomAD: Filtering AF: 0.001461 (no homozygotes)

    1. Case#: Patient UK22 (male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Mother is a carrier, two sisters (II:3, II:5) of patient UK22 were found to be carriers, niece of patient UK22 (III:4) is not a carrier

      ParentalTesting: Mother is a carrier, Father was unaffected (according to pedigree; figure 1)

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (<1% of factor IX; factor IX activity of 2 IU/dl), haemarthrosis of the knee, referred at 2 y/o,

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: Analysis of the essential regions of the gene; the promoter, exons, and regions containing the normal RNA processing signals only found this variant, and no other.

      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

    1. mutations

      Case#: VAN DE Water_NZ 2 (New Zealand, assumed male)

      DiseaseAssertion: Moderate Hemophilia B

      FamilyInfo: In 22 of the 32 families the mutation resulted in alteration of a restriction enzyme site. In these cases, researchers developed a rapid PCR based diagnosis assay, which eliminated the need for extensive family studies (enabled successful prenatal and carrier diagnostic studies to be undertaken in 22 subjects from five families)

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (2%)

      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

    1. mutations

      Case#: UK 130, Malmo 19, UK 134, Malmo 6, UK 129, Malmo 40, Malmo 20 (assumed male, from UK and Malmö, Sweden)

      DiseaseAssertion: UK 130: Moderate Hemophilia B Malmo 19: Moderate Hemophilia B UK 134: Severe Hemophilia B Malmo 6: Severe Hemophilia B UK 129: Moderate Hemophilia B Malmo 40: Moderate Hemophilia B Malmo 20: Moderate Hemophilia B

      FamilyInfo: None

      ParentalTesting: N/A

      CasePresentingHPOs: reduced factor IX activity

      CaseHPOsFreeText: UK 130 FIX:C: 1.6 Malmo 19 FIX:C: 2.3 ; FIX:AG: 36 UK 134 FIX:C: <1 Malmo 6 FIX:C: <1 ; FIX:AG: 26-35 UK 129 FIX:C: 4 Malmo 40 FIX:C: 1 ; FIX:AG: 30 Malmo 20 FIX:C: 2 ; FIX:AG: 27

      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

    1. c.109G>A (p.Ala37Thr)

      Case#: Odnoczko_Case (male, 74 y/o, in Poland)

      DiseaseAssertion: Severe Hemophilia B (only in patients who receive vitamin K antagnoists (VKAs). The authors believe that during VKA therapy, the FIX activity is much lower than that of other vitamin K-dependent clotting factors for cases with this variant.

      FamilyInfo: Family history of bleeding diathesis was negative

      ParentalTesting:

      CasePresentingHPOs: HP:0012233, HP:0031364, HP:0001892

      CaseHPOsFreeText: left thigh & buttock hematoma, ecchymosis on extremeties with no mucosal bleeding, bleeding diathesis

      CasePreviousTesting: local labaratory blood tests revealed anemia (hemoglobin concentration 8 g/dl; ref. range 14–18 g/dl), prolongation of prothrombin time (PT) with International Normalized Ratio (INR) within the therapeutic range (between 2.0 and 3.0). The proband's activated partial thromboplastin time (APTT) was significantly (>2-folds) prolonged and FIX activity markedly decreased

      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

    1. mutation

      Case#: Mutation found in 4 patients, and in 4 families

      DiseaseAssertion: Severe in 2 cases, moderate in the other 2 cases

      FamilyInfo: N/A

      ParentalTesting: None

      CasePresentingHPOs: HP:0011858, HP:0003645, HP:0001892

      CaseHPOsFreeText: reduced factor IX activity, activated partial thromboplastin time (APTT), normal FVIII clotting activity and bleeding tendency

      CaseNotHPOs: None

      CasePreviousTesting: N/A

      Gene: F9

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

      ClinVar: 811505

      CAID: CA414435537

      gnomAD: Absent/Not Reported

    1. Case#: Patient HB401 (Hispanic; Male)

      DiseaseAssertion: Moderate Hemophilia B

      FamilyInfo: None

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: FIX Coagulant Activity: 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

    1. Case#: Patient 63 (Spanish origin; assumed male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Not available

      ParentalTesting: Not available

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: FIX:C = 3 (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

    2. Case#: Patient 66 (Spanish origin; assumed male)

      DiseaseAssertion: Mild Hemophilia B

      FamilyInfo: Not available

      ParentalTesting: Not available

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: Factor IX: C = 30% (reduced factor IX activity)

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      Gene: F9

      Variant: NM_000133.4(F9):c.19A>T (p.Ile7Phe)

      LegacyVariant: c.48A>T (p.Ile-40Phe)

      ClinVar: 367997

      CAID: CA10529708

      gnomAD: Filtering AF: 0.0007752 (no homozygotes)

    3. Case#: Patient 72 (Spanish origin; assumed male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: Not available

      ParentalTesting: Not available

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: FIX:C = <1 (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: 811505

      CAID: CA414435537

      gnomAD: Absent/Not Reported

    1. c.110C > T p (Ala37Val).

      Case#: Mülling_Proband_1 (55 y/o, male)

      DiseaseAssertion: Severe Hemophilia B

      FamilyInfo: N/A

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0011858, HP:0100584, HP:0002094

      CaseHPOsFreeText: Reduced factor IX activity (FIX activity: 3%), infective endocarditis, dyspnea

      CaseNotHPOs: N/A

      CasePreviousTesting: N/A

      Gene: F9

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

      ClinVar: Absent

      CAID: CA414435437

      gnomAD: 0.00002186 in European (non-Finnish) population (highest frequency of variant found in this population)

      AdditionalCaseInfo: Patient developed severe bleeding under therapy with phenprocoumon, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors

    1. Variant

      Case#: Calgary 15

      DiseaseAssertion: Hemophilia B (severity not provided)

      FamilyInfo: None

      ParentalTesting: N/A

      CasePresentingHPOs: HP:0011858

      CaseHPOsFreeText: reduced factor IX activity (does not specify severity for probands) "patients from these kindreds have various disease severity, with plasma factor IX activity from < 0.01 U/mL to 0.30 U/mL." "FIX antigen was not available from patients from 6 kindreds, reduced in seven, normal in six, and not available from six."

      CaseNotHPOs: None

      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

  2. Aug 2026
  3. Dec 2025
  4. Mar 2025
  5. Jan 2025
  6. Dec 2024
  7. Oct 2024
    1. Die von Waldbränden außerhalb der Tropen verursachten Emissionen haben sich seit 2001 fast verdreifacht. Weltweit haben die Emissionen durch Waldbrände in dieser Zeit um 60% zugenommen. Ursache dafür ist die Kombination von heißerem und trockenerem Wetter mit dem schnelleren Wachstum der Wälder durch die höheren Temperaturen. Die Wälder können durch die Brände jahrzehntelang zu Emittenten werden. Damit ist die Funktion der Wälder als Kohlenstoffsenken gefährdet. Das bedeutet auch, dass sie andere anthropogene Emissionen weniger kompensieren und die Fähigkeit verlieren, nach einem Überschreiten der 1,5°-Grenze C0<sub>2</sub> aus der Atmosphäre zu entfernen. Außerdem müssten diese von Menschen verursachten Emissonen den C0<sub>2</sub>-Budgets der Nationalstaaten zugeordnet werden.

      https://theconversation.com/forest-fires-are-shifting-north-and-intensifying-heres-what-that-means-for-the-planet-241337

    1. Erstmals wurde genau erfasst, welcher Teil der von Waldbränden betroffenen Gebiete sich auf die menschlich verursachte Erhitzung zurückführen lässt. Er wächst seit 20 Jahren deutlich an. Insgesamt kompensieren die auf die Erhitzung zurückgehenden Waldbrände den Rückgang an Bränden durch Entwaldung. Der von Menschen verursachte – und für die Berechnung von Schadensansprüchen relevante – Anteil der CO2-Emissione ist damit deutlich höher als bisher angenommen https://www.carbonbrief.org/climate-change-almost-wipes-out-decline-in-global-area-burned-by-wildfires/

  8. Sep 2024
  9. Jul 2024
  10. Jun 2024
    1. for - Anthropocene - cross-scale spatial and temporal connectivity of water - governance - water - Anthropocene - cross scale - complexity - water governance - Anthropocene - from - Linked In post - new publication alart - to - Linked In post - new publication alert - Moving from fit to fitness for governing water in the Anthropocene

      summary - This is a good review paper that summarizes findings from two decades of water research on river basins and watersheds, - It highlights how recent Anthropocene research shows the global interconnected nature of water systems, - which makes the traditional River Basin Organization form of local governance challenging since - variability in localities far from the governed river basin or watershed can have significant impact on it and vice versa - New governance systems must emerge to deal with this complexity

      from - Linked In post - new publication alert - to - Linked In post - new publication alert - Moving from fit to fitness for governing water in the Anthropocene - https://hyp.is/GdXo1ipKEe-_FbMMhZGIMQ/www.linkedin.com/posts/activity-7207337444281659392-66RF/

  11. May 2024
    1. Linked Data in Production: Moving Beyond Ontologies

      Spring 2024 Member Meeting: CNI website • YouTube

      David Newbury Assistant Director, Software and UX Getty

      Over the past six years, Getty has been engaged in a project to transform and unify its complex digital infrastructure for cultural heritage information. One of the project’s core goals was to provide validation of the impact and value of the use of linked data throughout this process. With museum, archival, media, and vocabularies in production and others underway, this sessions shares some of the practical implications (and pitfalls) of this work—particularly as it relates to interoperability, discovery, staffing, stakeholder engagement, and complexity management. The session will also share examples of how other organizations can streamline their own, similar work going forward.

      http://getty.edu/art/collection/ http://getty.edu/research/collections/ http://vocab.getty.edu https://www.getty.edu/projects/remodeling-getty-provenance-index/

  12. Apr 2024
  13. Feb 2024
  14. Jan 2024
  15. Dec 2023
  16. Oct 2023
    1. The important part, as is so often the case with technology, isn’t coming up with a solution to the post portability problem, but coming up with a solution together so that there is mutual buy-in and sustainability in the approach.

      The solution is to not create keep creating these fucking problems in the first place.

  17. Sep 2023
    1. Hoekstra, a Shell man and a McKinsey man in charge of EU climate policy?
      • for: climate change policy hypocrisy, fossil fuel lobby, EU climate policy, Hoekstra, Fox guarding the henhouse, Linked In post
      • comment

        • What does it say about the EU's authenticity to deal with the global boiling crisis when they put a fox in charge of the henhouse?
        • this seems awfully similar to the choice for positioning an oil man to head COP28.
        • The fossil fuel lobby is EXTREMELY busy in the opaque back end of politics. We need more light to shine and bring the back end fossil fuel lobby activity out of the shadows to pre-empt future leadership betrayals.
      • future research

        • uncover future fossil fuel lobby’s game plan and future attempts to coopt climate change policy leadership
        • needed in order to proactively preempt the next attempt at coopting climate leadership. It’s difficult when we are simply reacting
    1. The Hyperdocument "Library System" where hyperdocuments can be submitted to a library-like service that catalogs them and guarantees access when referenced by its catalog number, or "jumped to" with an appropriate link. Links within newly submitted hyperdocuments can cite any passages within any of the prior documents, and the back-link service lets the online reader of a document detect and "go examine" any passage of a subsequent document that has a link citing that passage.

      That this isn't possible with open systems like the Web is well-understood (I think*). But is it feasible to do it with as-yet-untested closed (and moderated) systems? Wikis do something like this, but I'm interested in a service/community that behaves more closely in the concrete details to what is described here.

      * I think that this is understood, that is. That it's impossible is not what I'm uncertain about.

  18. Dec 2022
  19. Nov 2022
  20. Oct 2022
    1. Miller says he’s worried someone is creating a massive social network of bots for some future attack in which the automated accounts may be used to amplify false information online, or at least muddle the truth

      Maybe it's not the companies or potential scam victims that are the target here. Maybe it is the timeline that is the target. This would fit my own experience that the timeline has been deteriorating enormously, up to the point that I no longer allow the timeline to be visible in my profile. Unfollowd everyone.

  21. Aug 2022
    1. In practice, a system in which different parts of the web have different capabilities cannot insist on bidirectional links. Imagine, for example the publisher of a large and famous book to which many people refer but who has no interest in maintaining his end of their links or indeed in knowing who has refered to the book.

      Why it's pointless to insist that links should have been bidirectional: it's unenforceable.

  22. Jul 2022
    1. Documentazione

      Il problema di questa sezione è derubricare i modelli dati come documentazione. Le ontologie di ontopia (parlo di modelli non tanto di dati come i vocabolari controllati) sono machine-readable. Quindi non è solo una questione di documentare la sintassi o il contenuto del dato. È rendere il modello actionable, ossia leggibile e interpretabile dalle macchine stesse. Io potrei benissimo documentare dei dataset con una bella tabellina in Github o con tante tabelline in un bellissimo PDF (documentazione), ma non è la stessa cosa di rendere disponibile un'ontologia per dei dati. Rendere i modelli parte attiva della gestione del dato (come per le ontologie) significa abilitare l'inferenza che avete richiamato sopra in maniera impropria per me, ma anche utilizzarli per explainable AI e tanti altri usi. Questo è un concetto fondamentale che non può essere trattato così in linee guida nazionali. Dovrebbe anzi avere un capitolo suo dedicato, vista l'importanza anche in ottica data quality "compliance" caratteristica di qualità dello standard ISO/IEC 25012.

    2. Nel caso a), il soggetto ha tutti gli elementi per rappresentare il proprio modello dati; viceversa, nei casi b) e c), la stessa amministrazione, in accordo con AgID, valuta l’opportunità di estendere il modello dati a livello nazionale.

      Tutta la parte di modellazione dati, anche attraverso il catalogo nazionale delle ontologie e vocabolari controllati, sembra ora in mano a ISTAT, titolare, insieme al Dipartimento di Trasformazione Digitale di schema.gov.it. Qui però sembra AGID abbia il ruolo di definire i vari modelli. Secondo me questo crea confusione. bisognerebbe coordinarsi anche con le altre amministrazioni per capire bene chi fa cosa. AGID al momento di OntoPiA gestisce solo un'infrastruttura fisica.

    3. Utilizzando il framework RDF, si può costruire un grafo semantico, noto anche come grafo della conoscenza, che può essere percorso dalle macchine risolvendo, cioè dereferenziando, gli URI HTTP. Ciò significa che è possibile estrarre automaticamente informazione e derivare, quindi, contenuto informativo aggiuntivo (inferenza).

      Non è che fate inferenza perché dereferenziate gli URI. Vi suggerisco di leggere bene le linee guida per l'interoperablità semantica attraverso i linked open data che spiega cosìè l'inferenza (e questa sì fa parte di un processo di arricchimento nel mondo linked open data). L'inferenza è una cosa più complessa che si può fare con ragionatori automatici e query sparql. Si possono dedurre nuove informazioni dati dati esistenti e soprattutto dalle ontologie che sono oggetti machine readable!

  23. Jun 2022
    1. È importante notare che nella pratica si ritiene a volte necessario passare da modelli di rappresentazione tradizionali come quello relazionale per la modellazione dei dati operando opportune trasformazioni per poi renderli disponibili secondo i principi dei Linked Open Data. Tuttavia, tale pratica non è necessariamente quella più appropriata: esistono situazioni per cui può essere più conveniente partire da un’ontologia del dominio e che si intende modellare e dall’uso di standard del web semantico per poter governare i processi di gestione dei dati.

      Non trovo utilità in quanto qui scritto onestamente. Molti più sistemi sono ormai linked open data nativi, quindi oltre al fatto che parlare di linked open data in arricchimento è sbagliato, direi di lasciar perdere questo periodo.

    2. a formati di dati a quattro stelle come le serializzazioni RDF o il JSON-LD

      JSON-LD è una serializzazione RDF nel mondo JSON. Occhio che qui la traduzione in italiano del documento del publications office non è venuta fuori bene (loro dicono data format such as RDF or JSON-LD che sarebbe anche impreciso. RDF è un modello di rappresentazione del dato nel Web. Le serializzazioni RDF sono tipo Ntriple, RDF/Turtle, RDF/XML, JSON-LD). Tra l'altro nell'allegato tecnico sui formati per i dati aperti, testo preso dalla precedente linee guida, JSON-LD è indicato come serializzazione RDF.

    3. il linking è una funzionalità molto importante e di fatto può essere considerata una forma particolare di arricchimento. La particolarità consiste nel fatto che l’arricchimento avviene grazie all’interlinking fra dataset di origine diversa, tipicamente fra amministrazioni o istituzioni diverse, ma anche, al limite, all’interno di una stessa amministrazione”

      Qui c'è un problema di fondo proprio concettuale. Il problema è che il paradigma dei Linked Open Data è stato derubricato come arricchimento, che nelle linee guida che si cita qui era solo una fase di un processo generale per la gestione dei dati linked open data. Fare linked open data non vuol solo dire arricchire i dati, ma è possibile gestire un dato fin dalla sua nascita in linked open data nativamente. Questo era lo spirito delle linee guida qui citate. Estrapolando solo una parte avete snaturato un po' tutto. Consiglio di trattare l'argomento com'era trattato nelle precedenti linee guida. Peccato anche che sia sparita la figura della metropolitana che aiutava molto.

    4. Come detto, il collegamento (linking) dei dati può aumentarne il valore creando nuove relazioni e consentendo così nuovi tipi di analisi.

      Comunque, farei uno sforzo in più, con tutto quello che l'italia ha scritto sui linked open data, per scrivere frasi che non siano proprio paro paro la traduzione in italiano del documento in inglese.

    1. Energy efficiency has never been more crucial! The time to unleashing its massive potential has come

      Will this conference debate rebound effects of efficiency? If not, it will not have the desirable net effect.

      My linked In comments were:

      Alessandro Blasi, will this conference address the rebound effect? In particular, Brockway et al. have done a 2021 meta-analysis of 33 research papers on rebound effects of energy efficiency efforts and conclude:

      "...economy-wide rebound effects may erode more than half of the expected energy savings from improved energy efficiency. We also find that many of the mechanisms driving rebound effects are overlooked by integrated assessment and global energy models. We therefore conclude that global energy scenarios may underestimate the future rate of growth of global energy demand."

      https://www.sciencedirect.com/science/article/pii/S1364032121000769?via%3Dihub

      Unless psychological and sociological interventions are applied along with energy efficiency to mitigate rebound effects, you will likely and ironically lose huge efficiencies in the entire efficiency intervention itself.

      Also, as brought up by other commentators, there is a difference between efficiency and degrowth. Intelligent degrowth may work, especially applied to carbon intensive areas of the economy and can be offset by high growth in low carbon areas of the economy.

      Vaclav Smil is pessimistic about a green energy revolution replacing fossil fuels https://www.ft.com/content/71072c77-53b3-4efd-92ae-c92dc02f09ad, which opens up the door to serious consideration of degrowth, not just efficiency improvements. Perhaps the answer is in a combination of all of the above, including targeted degrowth.

      Technology moves quickly and unexpectedly. At the time of Smil's book release, there was no low carbon cement. Now there is a promising breakthrough: https://www.cnbc.com/2022/04/28/carbon-free-cement-breakthrough-dcvc-put-55-million-into-brimstone.html

      As researchers around the globe work feverishly to make low carbon breakthroughs, there is obviously no guarantee of when they will occur. In that case then, with only a few years to peak, it would seem the lowest risk pathway would be to prioritize the precautionary principle over a gambling pathway (such as relying on Negative Emissions Technology breakthroughs) and perhaps consider along with rebound effect conditioned efficiency improvements also include a strategy of at least trialing a temporary, intentional degrowth of high carbon industries / growth of low carbon industries.

    1. Perhaps one of the most important questions to be asked is “What are we not ‘seeing’?.” … “A collaborative project of the late botanists Erwin Lichtenegger and Lore Kutschera celebrates the power and beauty of these otherwise hidden systems through detailed drawings of agricultural crops, shrubs, trees, and weeds. Digitized by the Wageningen University & Research, the extensive archive is the culmination of 40 years of research in Austria that involved cultivating and carefully retrieving developed plant life from the soil for study. It now boasts more than 1,000 renderings of the winding, spindly roots, some of which branch multiple feet wide.”

      These drawings are metaphors for the human meaningverse of an individual and the visible and invisible aspects of our ideas that we present to the rest of the world.

      What is of greatest meaning lives in the individual's salience landscape. That salience landscape is the result of a lifetime of sense-making - all the books we've ever read, talks or presentations we've ever listened to, conversations we've had, courses we've studied. While the other person may have an idea of what is important to us, they are clueless of how that salience landscape came to be.

      This vast network of formative events is usually invisible to the OTHER.

      The public, open source Indyweb that is currently being designed will allow the individual user for the first time to consolidate all his or her digital learning in one place, the user's owned Indyhub. Since Indyweb also has built-in provenance, it will allow traceability of public ideas. This allows the individual to keep track of what would otherwise by invisible and lost - the history of his/her social interaction with ideas.

    1. What can we do with a shift in thinking backed by a total of $3.6 trillion in funds under management? I’m backing strategic circular initiatives to convert the highest return on value for anyone’s money. Stay tuned as we crack open new investment opportunities.

      Her diagram explicitly shows a synthesis of planetary boundaries and circular economy. This is a connection that many in this area are tacitly aware of but is good to explicate it in a diagram of this sort..

      If circular economy is about ultimate reuse and recirculating material flows to eliminate the concept of waste, then how does energy consumption fit into the picture? Obviously, CO2 emissions is a form of material waste that is an undesirable byproduct of carbon-based energy usage. Capturing CO2 and reusing it is one method, but not a very scalable solution presently.

    1. What happens in Indonesia when a textile manufacturer illegally dumps dye waste!

      This is an example of the manufacturer / consumer dualism created by the Industrial Revolution. Since manufacturers have become a separate layer that no longer exist as part of the community, as artisans once did, along with globalized capitalism, the consumer does not know the life history of the product being consumed. The sensory bubble limits what a consumer can directly know.

      One answer is to promote a trend back to local and artisan production. Relocalizing production can empower consumers to inspect producers of the products they consume, holding them accountable.

      Another answer is to develop globalized trust networks of producers who are truly ethical.

      Cosmolocal production has networks by the commons nature can promote such values.

  24. Apr 2022
  25. Mar 2022
  26. Feb 2022
    1. Wordle's spread on social media was enabled in part by its low-tech approach for e.g. sharing scores.

      One low-tech approach that could've been used here for data persistence would be to generate and prompt the user to save their latest scorecard in PDF or Word format—only it's not a PDF or Word format, but instead "wordlescore.html" file, albeit one that they are able to save to disk and double click to open all the same. When they need to update their scorecard with today's data, you use window.open to show a page that prompts the user to open their most recent scorecard (using either Ctrl+/Cmd+O, or by navigating to the place where they saved it on disk via bookmark). What's not apparent on sight alone is that their wordlescore.html also contains a JS payload as an inline script. When wordlescore.html is opened, it's able to communicate with the Wordle tab via postMessage to window.opener, request the newest data from the app, and then update wordlescore.html itself as appropriate.

    1. Darüber hinaus ist ein wichtiger Trend Linked Data im Unternehmensumfeld zu etablieren, um eine neue Generation semantischer, vernetzter Daten-Anwendungen auf Basis des Linked Data Paradigmas zu entwickeln, zu etablieren und erfolgreich zu vermarkten. Im BMBF Wachstumskernprojekt „Linked Enterprise Data Services“ entsteht hierfür beispielsweise eine Technologieplattform, die es Unternehmen ermöglichen soll, neue Dienstleistungen im Web 3.0 zu etablieren.

      BMBF Wachstumskernprojekt „Linked Enterprise Data Services

    1. Eine wesentliche Idee von Linked Data ist es, dass Daten und Informationen un-terschiedlichster Herkunft und Struktur auf Basis von Standards interpretiert, (weiter-)verarbeitet, verknüpft und schließlich dem User in einer Form präsentiert werden können,sodass dieser seine Aufwände zur Informationsgewinnung und -aufbereitung verringernkann

      Leitidee von Linked Data

  27. Jan 2022
  28. Dec 2021
    1. I buy domains on a regular basis and often from more than one registrar because of a better deal or TLD availability. As a result, I tend to forget I have some domains! True story, I once ran a WHOIS search on a domain I own.

      The subtext here is, "that's why i created BeachfrontDigital". But this shows how "apps" (and systems) have poisoned how we conceptualize problems and their solutions.

      The simplest solution to the problem described is a document, not a never-finished/never-production-ready app. Bespoke apps have lots of cost overhead. Documents, on the other hand—even documents with rich structure—are cheap.

  29. Aug 2021
    1. One thing I'd like forward-looking hypertext toolmakers to keep in mind is the ability for the tools to help people answer questions like "What led to legalanthology.ch hosting a copy of this document? Given a URL from one organization, is it possible to look at the graph of internal backlinks (let me focus narrowly on incoming edges originating from the same host)?"

  30. Jun 2021
  31. May 2021
  32. Jan 2021
    1. Why is CORS important? Currently, client-side scripts (e.g., JavaScript) are prevented from accessing much of the Web of Linked Data due to "same origin" restrictions implemented in all major Web browsers. While enabling such access is important for all data, it is especially important for Linked Open Data and related services; without this, our data simply is not open to all clients. If you have public data which doesn't use require cookie or session based authentication to see, then please consider opening it up for universal JavaScript/browser access. For CORS access to anything other than simple, non auth protected resources
  33. Sep 2020
  34. Jul 2020