Case#: Oldenburg_Patient_A and Oldenburg_Patient_C

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

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

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858

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

CaseNotHPOs: N/A

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: Absent

CAID: CA414435437

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

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

DiseaseAssertion: Severe Hemophilia B

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

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858, HP:0012233

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

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: Absent

CAID: CA414435437

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

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

DiseaseAssertion: Severe Hemophilia B

FamilyInfo: N/A

ParentalTesting: N/A

CasePresentingHPOs: HP:0011858, HP:0012233

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

CaseNotHPOs: None

CasePreviousTesting: N/A

Gene: F9

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

ClinVar: Absent

CAID: CA414435437

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

Case#: 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