PMID: 27177407

Gene: F9

HGNCID: 3551

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

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

PMID: 31904612

Gene: F9

HGNCID: 3551

PMID: 8365725

Gene: F9

HGNCL: 3551

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

PMID: 16643212

Gene: F9

HGNC: 3551

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

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

PMID: 19236374

Gene: F9

HGNC: 3551

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

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

PMID: 28722788

Gene: F9

HGNC: 3551

PMID: 27213901

Gene: F9

HGNC: 3551

PMID: 34187575

Gene: F9

HGNC: 3551

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

PMID: 12588353

Gene: F9

HGNC: 3551

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#: 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#: 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

PMID: 3009023

Gene: F9

HGNC: 3551

Case#: Family HB90

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

CaseHPOsFreeText: reduced factor IX activity (FIX:C:4 (post therapy values but clinically severe by criteria of Eyster et al. (1980)

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

AdditionalCaseInfo: Previously reported by Giannelli et al. (1990)

PMID:

Gene: F9

HGNCID: 3551

Case#: B21 (assumed male, Indian origin)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: None

ParentalTesting: N/A

CasePresentingHPOs: reduced factor IX activity (FIX:C: 1.3%)

CaseHPOsFreeText: HP:0011858

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#: 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#: 47

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: FIX:C 18/26% (Mild Phenotype)

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

Gene: F9

Variant: NM_000133.3(F9):c.835G>A (p.Ala279Thr)

ClinVar: 216926 https://www.ncbi.nlm.nih.gov/clinvar/variation/216926/

CAID: CA277507

gnomAD: Not reported

PMID: 22544209

Gene: F9

HGNC: 3551

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

PMID: 21118338

Gene: F9

HGNC: 3551

PMID: 31026269

Gene: F9

HGNC: 3551

Case1: 3-year-old boy

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: The pathogenic mutation of F9 gene in this family was identified, Mother and Grandmother are HB carriers, Father tested negative. Pedigree shown in Figure 1.

ParentalTesting: Sequences at the mutation locus in F9 genes were analyzed by Sanger sequencing.

CasePresentingHPOs: NA

CaseHPOFreeText: Hemorrhagic spots on his skin at birth, Gingival bleeding, APTT 66.5 s, FIX:C < 1%, FVIII:C 116.8%

CasePreviousTesting: PCR amplification for coding and flanking sequences of F9 gene, PCR amplification products sequenced by Songon Biotech Co. Ltd.

Gene: F9

Variant: NM_000133.3:c.1232G>C (p.Ser411Thr)

ClinVar: NA

CAID: CA414446686

gnomAD: NA

PMID: 31124946

Gene: F9

HGNCID: 3551

PMID:

Gene: F9

HGNC: 3551

Case#: UQU-HB3, Male, 1-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Severe, PTT 50.9, Disabled left ankle

CasePreviousTesting: Screened for all factor IX exons by capillary sequencing

Gene: F9

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

ClinVar: NA

CAID: CA414441211

gnomAD: Not reported

Case#: UQU-HB9, Male, 1-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: NA

CaseHPOFreeText: Moderate, PTT 51.4, Unable to flex knees fully

CasePreviousTesting: Screened for all factor IX exons by capillary sequencing

Gene: F9

Variant: NM_001313913.1:c.580G>A

ClinVar: NA

CAID: CA414441211

gnomAD: Not reported

Case#: UQU-HB11, Male, 1-months-old, Saudi Arabia

DiseaseAssertion: Hemophilia B

FamilyInfo: NA

ParentalTesting: NA

CasePresentingHPOs: HP:0001892 (Abnormal bleeding)

CaseHPOFreeText: Severe, Unable to flex elbows fully, PTT 148.3

CasePreviousTesting: Screened for all factor IX exons by capillary sequencing

Gene: F9

Variant: NM_000133.4(F9):c.855G>C (p.Glu285Asp)

ClinVar: 828138 https://www.ncbi.nlm.nih.gov/clinvar/variation/828138/

CAID: CA414444506

gnomAD: Not reported

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

PMID: 30576981

Gene: F9

HGNC: 3551

PMID: 24375831

Gene: F9

HGNC: 3551

PMID: 1615486

Gene: F9

HGNC: 3551

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

PMID: 8772212

Gene: F9

HGNC: 3551

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

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)

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

PMID: 10595634

Gene: F9

HGNC: 3551

PMID: 1897528

Gene: F9

HGNC: 3551

Case#: HB-125 (assumed male, India)

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: None

CasePresentingHPOs: HP:0011858

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

CaseNotHPOs: None

CasePreviousTesting: None

Gene: F9

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

ClinVar: 810864

CAID: CA414435539

gnomAD: Absent/Not Reported

PMID: 30846504

Gene: F9

HGNC: 3551

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

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#: 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

PMID: 29923114

Gene: F9

HGNC: 3551

PMID: None

Gene: F9

HGNC: 3551