c.706G>C
Case#: 46
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 4% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.706G>C (p.Gly236Arg)
ClinVar: NA
CAID: CA414441294
gnomAD: Not reported
c.95T>C
Case#: 39
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 19% (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:c.95T>C (p.Leu32Pro)
ClinVar: NA
CAID: CA414435358
gnomAD: Not reported
c.1345C>T
Case#: 43
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 30% (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.1345C>T (p.Arg449Trp)
ClinVar: 626990 https://www.ncbi.nlm.nih.gov/clinvar/variation/626990/
CAID: CA10529890
gnomAD: MAF for Arg449Trp in the European (non-Finnish) population 0.00006494<br>https://gnomad.broadinstitute.org/variant/X-138644189-C-T?dataset=gnomad_r2_1
c.1274T>A
Case#: 42
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 10% (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:c.1274T>A (p.Leu425Ter )
ClinVar: NA
CAID: CA414446997
gnomAD: Not reported
c.689G>A
Case#: 45
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 5% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.689G>A (p.Gly230Glu)
ClinVar: NA
CAID: CA414441179
gnomAD: Not reported
c.1291T>G
Case#: 41
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 2/2% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.1291T>G (p.Trp431Gly)
ClinVar: NA
CAID: CA414447127
gnomAD: Not reported
c.1219T>C
Case#: 40
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.1219T>C (p.Cys407Arg)
ClinVar: NA
CAID: CA414446562
gnomAD: Not reported
c.518C>T
Case#: 43
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.518C>T (p.Ala173Val)
ClinVar: NA
CAID: CA414439510
gnomAD: Not reported
c.422G>A
Case#: 42
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 4% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.4(F9):c.422G>A (p.Cys141Tyr)
ClinVar: 811510 https://www.ncbi.nlm.nih.gov/clinvar/variation/811510/
CAID: CA414438897
gnomAD: Not reported
c.226G>C
Case#: 41
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.226G>C (p.Glu76Gln)
ClinVar: NA
CAID: CA414436160
gnomAD: Not reported
c.1052G>A
Case#: 39
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.1052G>A (p.Gly351Asp)
ClinVar: NA
CAID: CA414445595
gnomAD: Not reported
c.1025C>T
Case#: 48
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 3% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3(F9):c.1025C>T (p.Thr342Met)
ClinVar: 10607 https://www.ncbi.nlm.nih.gov/clinvar/variation/10607/
CAID: CA255381
gnomAD: Not reported
c.835G>A
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
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
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
6.
Case#: 6
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 11%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.316G>A
LegacyVariant:
ClinVar: No
CAID: CA255329
gnomAD:
27.
Case#: 27
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1244A>G
LegacyVariant:
ClinVar: No
CAID: CA414446777
gnomAD:
43.
Case#: 43
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.252+2T>C
LegacyVariant:
ClinVar: No
CAID: CA414436438
gnomAD:
13.
Case#: 13
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 6.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.797C>T
LegacyVariant:
ClinVar: No
CAID: CA414443482
gnomAD:
34.
Case#: 34
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.223C>T
LegacyVariant:
ClinVar: No
CAID: CA340993
gnomAD:
19.
Case#: 19
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1129G>T
LegacyVariant:
ClinVar: No
CAID: CA414446072
gnomAD:
26.
Case#: 26
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1234G>T
LegacyVariant:
ClinVar: No
CAID: CA414446705
gnomAD:
42.
Case#: 42
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.252+2T>G
LegacyVariant:
ClinVar: No
CAID: CA414436440
gnomAD:
18.
Case#: 18
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1068G>T
LegacyVariant:
ClinVar: No
CAID: CA414445683
gnomAD:
33.
Case#: 33
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.103G>T
LegacyVariant:
ClinVar: No
CAID: CA414435383
gnomAD:
25.
Case#: 25
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1204G>A
LegacyVariant:
ClinVar: No
CAID: CA414446446
gnomAD:
12.
Case#: 12
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.761G>A
LegacyVariant:
ClinVar: No
CAID: CA414443235
gnomAD:
5
Case#: 5
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.305G>T
LegacyVariant:
ClinVar: No
CAID: CA414437422
gnomAD:
41.
Case#: 41
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1135C>T
LegacyVariant:
ClinVar: No
CAID: CA255391
gnomAD:
17.
Case#: 17
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1025C>T
LegacyVariant:
ClinVar: No
CAID: CA255381
gnomAD:
40.
Case#: 40
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.892C>T
LegacyVariant:
ClinVar: No
CAID: CA255370
gnomAD:
4.
Case#: 4
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.160G>C
LegacyVariant:
ClinVar: No
CAID: CA414435755
gnomAD:
24.
Case#: 24
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1193G>A
LegacyVariant:
ClinVar: No
CAID: CA414446384
gnomAD:
29.
Case#: 29
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1279G>A
LegacyVariant:
ClinVar: No
CAID: CA414447040
gnomAD:
11.
Case#: 11
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.677G>A
LegacyVariant:
ClinVar: No
CAID: CA121128
gnomAD:
39.
Case#: 39
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.892C>T
LegacyVariant:
ClinVar: No
CAID: CA255370
gnomAD:
32.
Case#: 32
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1306G>A
LegacyVariant:
ClinVar: No
CAID: CA414447233
gnomAD:
23.
Case#: 23
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1193G>A
LegacyVariant:
ClinVar: No
CAID: CA414446384
gnomAD:
3.
Case#: 3
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.128G>A
LegacyVariant:
ClinVar: No
CAID: CA414435539
gnomAD:
16.
Case#: 16
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 12%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.881G>A
LegacyVariant:
ClinVar: No
CAID: CA255368
gnomAD:
10.
Case#: 10
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 2.5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.571C>T
LegacyVariant:
ClinVar: No
CAID: CA255340
gnomAD:
38.
Case#: 38
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.719G>A
LegacyVariant:
ClinVar: No
CAID: CA414441403
gnomAD:
31.
Case#: 31
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1291T>A
LegacyVariant:
ClinVar: No
CAID: CA414447125
gnomAD:
22
Case#: 22
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1145G>A
LegacyVariant:
ClinVar: No
CAID: CA414446163
gnomAD:
2.
Case#: 2
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.127C>T
LegacyVariant:
ClinVar: No
CAID: CA414435537
gnomAD:
1.
Case#: 1
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.88G>A
LegacyVariant:
ClinVar: No
CAID: CA414434500
gnomAD:
30.
Case#: 30
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1291T>C
LegacyVariant:
ClinVar: No
CAID: CA414447130
gnomAD:
9.
Case#: 9
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.533G>A
LegacyVariant:
ClinVar: No
CAID: CA414440301
gnomAD:
37.
Case#: 37
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.655C>T
LegacyVariant:
ClinVar: No
CAID: CA255347
gnomAD:
8.
Case#: 8
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.422G>A
LegacyVariant:
ClinVar: No
CAID: CA414438897
gnomAD:
21.
Case#: 21
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1136G>A
LegacyVariant:
ClinVar: No
CAID: CA255394
gnomAD:
15.
Case#: 15
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 3.5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.881G>A
LegacyVariant:
ClinVar: No
CAID: CA255368
gnomAD:
14.
Case#: 14
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 10%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.835G>A
LegacyVariant:
ClinVar: No
CAID: CA277507
gnomAD:
44.
Case#: 44
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.253-2A>G
LegacyVariant:
ClinVar: No
CAID: CA414436483
gnomAD:
20.
Case#: 20
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1136G>A
LegacyVariant:
ClinVar: No
CAID: CA255394
gnomAD:
49.
Case#: 49
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.862_863delGA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
7.
Case#: 7
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.344A>G
LegacyVariant:
ClinVar: No
CAID: CA414437636
gnomAD:
28.
Case#: 28
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All relevant sequences of F9 were PCR amplified and analyzed by DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1274T>C
LegacyVariant:
ClinVar: No
CAID: CA414447009
gnomAD:
1
Case#: 1
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1324G>A
LegacyVariant:
ClinVar: No
CAID: CA255418
gnomAD:
6
Case#: 6
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.1307C>A
LegacyVariant:
ClinVar: No
CAID: CA255413
gnomAD:
17
Case#: 17
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.172G>C
LegacyVariant:
ClinVar: No
CAID: CA414435830
gnomAD:
8
Case#: 8
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.349T>C
LegacyVariant:
ClinVar: No
CAID: CA414437669
gnomAD:
16
Case#: 16
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1.5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.427C>G
LegacyVariant:
ClinVar: No
CAID: CA414438921
gnomAD:
11
Case#: 11
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.676C>T
LegacyVariant:
ClinVar: No
CAID: CA255350
gnomAD:
20
Case#: 20
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.252+1G>A
LegacyVariant:
ClinVar: No
CAID: CA414436412
gnomAD:
2
Case#: 2
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.391+1G>C
LegacyVariant:
ClinVar: No
CAID: CA414438024
gnomAD:
15
Case#: 15
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 2.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.781T>C
LegacyVariant:
ClinVar: No
CAID: CA414443378
gnomAD:
10
Case#: 10
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1.8%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant:
LegacyVariant: NM_000133.3:c.880C>T
ClinVar: No
CAID: CA255344
gnomAD:
4
Case#: 4
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.520G>C
LegacyVariant:
ClinVar: No
CAID: CA414439517
gnomAD:
19
Case#: 19
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 1.9%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.755G>A
LegacyVariant:
ClinVar: No
CAID: CA414443205
gnomAD:
7
Case#: 7
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.677G>A
LegacyVariant:
ClinVar: No
CAID: CA121128
gnomAD:
18
Case#: 18
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 3.9%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.284A>G
LegacyVariant:
ClinVar: No
CAID: CA414437372
gnomAD:
14
Case#: 14
DiseaseAssertion: Hemophilia B, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.59T>C
LegacyVariant:
ClinVar: No
CAID: CA414434363
gnomAD:
3
Case#: 3
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.881G>A
LegacyVariant:
ClinVar: No
CAID: CA255368
gnomAD:
9
Case#: 9
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 5.1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.172G>C
LegacyVariant:
ClinVar: No
CAID: CA414435830
gnomAD:
c.128G>A
Case#: Variant #24 (no specific case; 5 patients and 5 families have variant)
DiseaseAssertion: Severe (2), Moderate (1), Mild (2)
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: Absent/Not Reported
CAID: CA414435539
gnomAD: Absent/Not Reported
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
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
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
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
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
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
H (karachi
Case#: Nawaz_Proband_H (karachi) (Pakistan resident)14 y/o)
DiseaseAssertion: Hemophilia B (no severity assertion made)
FamilyInfo: None
ParentalTesting: None
CasePresentingHPOs: N/A
CaseNotHPOs: N/A
CasePreviousTesting: None
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
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
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
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
Twenty-five novel mutations of the factor IX gene in haemophilia B
Case#: Wulff_Proband_2252 and Wulff_Proband_2270
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>T (p.Arg43Leu)
ClinVar: 993549
CAID: CA414435545
gnomAD: Absent/Not Reported
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
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
mutations
Case#: Wulff_Proband_031 & Wulff_Proband_048
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (Proband_031: FIX:C: <1 FIX:Ag: 48 ; Proband_048 FIX:C <1 FIX:Ag: 52
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
The proband, 12-year-old boy with moderate bleeding history, had manifest prolonged activated partial thromboplastin time (98.1 s) and markedly decreased FIX activity (1%).
Case#: 12 year old male
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: Uncle had mild Hemophilia B
ParentalTesting: No
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: exons and introns were amplified by PCR and subsequently analyzed by direct sequencing
Gene: F9
Variant:
LegacyVariant:
ClinVar:
CAID:
gnomAD:
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
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
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
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
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
(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
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
6 months of age, the proband (male, born on 20 February 2008)
Case2: 6-month-old Male, China
DiseaseAssertion: Hemophilia B (Factor IX-deficient)
FamilyInfo: Mother and maternal grandmother are HB carriers due to a novel mutation in intron 3. Pedigree shown in Figure 1.
ParentalTesting: The F9 exons were amplified (RT-PCR) and exons 1 to 8 of the F9 gene were analyzed with the ABI 3130 Genetic Analyzer, Sequenced intron 3 of the F9 gene
CasePresentingHPOs: HP:0011858 (Reduced factor IX activity)
CaseHPOFreeRext: FIX:C 1%, Pelioma, Cyanotic bumps, Subcutaneous bleeding, knee swelling from crawling
CasePreviousTesting: Prenatal testing at 20 weeks
Gene: F9
Variant: NM_000133.3(F9):c.278-3A>G
ClinVar: 92225 https://www.ncbi.nlm.nih.gov/clinvar/variation/92225/#id_first
CAID: CA285284
gnomAD: Not Reported
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
HB55
Case#: Family HB55
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1)
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>T (p.Arg43Leu)
ClinVar: 993549
CAID: CA414435545
gnomAD: Absent/Not Reported
mutations in the factor IX gene resulting in hemophilia B
Case#: Gostout_Proband_189 (assumed male, Asian (from India))
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: 3%)
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
LegacyVariant: c.6364C>T (p.Arg-4Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
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
UQU-HB4
Case#: UQU-HB4, Male, 6-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, PTT 60.1
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.1025C>T (p.Thr342Met)
ClinVar: 10607 https://www.ncbi.nlm.nih.gov/clinvar/variation/10607/
CAID: CA255381
gnomAD: Not reported
UQU-HB2
Case#: UQU-HB2, Male, 2-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, PTT 74.5, Disabled right knee
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A (p.Asp194Asn)
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
UQU-HB1
Case#: UQU-HB1, Male, 2-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, PTT 74.5
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.1136G>A (p.Arg379Gln)
ClinVar: 10613 https://www.ncbi.nlm.nih.gov/clinvar/variation/10613/
CAID: CA255394
gnomAD: Not reported
UQU-HB7
Case#: UQU-HB7, Male, 16-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Disabled right knee and both ankles , PTT 53.2
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.880C>T (p.Arg294Ter)
ClinVar: 10587 https://www.ncbi.nlm.nih.gov/clinvar/variation/10587/
CAID: CA255344
gnomAD: Not reported
UQU-HB5
Case#: UQU-HB5, Male, 12-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, PTT 47.3
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.316G>A (p.Gly106Ser)
ClinVar: 10579 https://www.ncbi.nlm.nih.gov/clinvar/variation/10579/
CAID: CA255329
gnomAD: MAF for Gly106Ser in the Other population 0.0001881<br>https://gnomad.broadinstitute.org/variant/X-138623273-G-A?dataset=gnomad_r2_1
UQU-HA33
Case#: UQU-HA33, Male, 2-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 99.5, Disabled Right Knee, Severe
CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons
Gene: F8
Variant: NM_000132.3:c.760A>G (p.Asn254Asp)
ClinVar: NA
CAID: CA414918977
gnomAD: Not reported
UQU-HB6
Case#: UQU-HB6, Male, 11-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Disabled right knee, PTT 52.2
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.880C>T (p.Arg294Ter)
ClinVar: 10587 https://www.ncbi.nlm.nih.gov/clinvar/variation/10587/
CAID: CA255344
gnomAD: Not reported
Hb15
Case#: HB15 (assumed male, Tunisian)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: None
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX: <1)
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
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
(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
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
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
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
6364 C→T
Case#: Ivaskevicius_Proband_LT65 (assumed male, Lithuanian)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: 0)
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
LegacyVariant: c.6364C>T (p.Arg-4Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
Table S1
Case#: Li_Proband_1 (male)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: Not provided
ParentalTesting: Not provided
CasePresentingHPOs: N/A
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.82T>C (p.Cys28Arg)
ClinVar: 10657
CAID: CA255450
gnomAD: Absent/Not Reported
Case#: Patient A (assumed male)
DiseaseAssertion: Severe (sporadic) Hemophilia B
FamilyInfo: Variant also localized in affected brother, mother (Native American descent) is deceased but maternal grandmother and two maternal aunts screened negative, researchers believe this de novo mutation originated during either grandparent’s gametogenesis.
ParentalTesting: Mother deceased, no mention of father
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: FIX Clotting Activity (U/dl): < 1, Antigen Level (U/dl): < 1
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.50T>A (p.Ile17Asn)
LegacyVariant: c.79T>A (p.Ile-30Asn)
ClinVar: Absent
CAID: CA414434315
gnomAD: Absent/Not Reported
Case#: Liu_Proband_56/439/440/486/830 (assumed male; Chinese)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: Absent
CAID: CA414435539
gnomAD: Absent/Not Reported
Case#: Liu_Proband_438 (assumed male; Chinese)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
ClinVar: Absent
CAID: CA414435537
gnomAD: Absent/Not Reported
Case#: Liu_Proband_316 (assumed male; Chinese)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.82T>G (p.Cys28Gly)
ClinVar: Absent
CAID: CA414434482
gnomAD: Absent/Not Reported
Case#: Liu_Proband_322 (assumed male; Chinese)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.59T>C (p.Leu20Ser)
ClinVar: Absent
CAID: CA414434363
gnomAD: Absent/Not Reported
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
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
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
c.83G>A/p.Cys28Tyr
Case#: Nummi_Proband_6 (assumed male)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0001929 (FIX baseline clotting activity: 1
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.83G>A (p.Cys28Tyr)
ClinVar: Absent
CAID: CA414434483
gnomAD: Absent/Not Reported
Case#: Oldenburg Cases A, B and C (A: 66 y/o, B: 38 y/o, C: 30 y/o (all in Germany))
DiseaseAssertion: Mild Hemophilia B
FamilyInfo: No bleeding tendency noted in any of these patients family history
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: severe bleeding at each occasion of oral anticoagulation with phenoprocoumon, bleeding was located in the muscles of the upper leg (patients A and C) and scrotum, left calf and thigh musles (patient B), reduced factor IX levels
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.109G>A (p.Ala37Thr)
LegacyVariant: p.Ala-10Thr
ClinVar: 804089
CAID: CA10529736
gnomAD: Allele Frequency in population where variant was found in the highest (South Asian population): 0.0001128
AdditionalCaseInfo: all patients were unrelated up to the third generation. However, the parents of patients A and C emigrated from the same region in North-Eastern Europe (North Poland)
Table 1
Case#: Cz14, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3(F8):c.5953C>T (p.Arg1985Ter)
ClinVar: 10300 https://www.ncbi.nlm.nih.gov/clinvar/variation/10300/
CAID: CA255191
gnomAD: Not reported
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
.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
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
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
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
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
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
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
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
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
Fig. 1
Case#: 12 year old male
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: Mother was a carrier. Maternal uncle has the same hemizygous mutation
ParentalTesting: Family Pedigree reveals that the mother was a carrier of the variant identified in the proband
CasePresentingHPOs: HP:0011858, HP:0030839
CaseHPOFreeText: FIX:C = 1%, proband had a history of soft tissue hemorrhages since 7 years of age
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Direct nucleotide sequencing was completed
Gene: F9
Variant: NM_000133.3:c.157G>C
LegacyVariant:
ClinVar: No
CAID: CA414435729
gnomAD:
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)
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
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
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
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
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
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
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
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
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
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
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
mutations
Case#: Tartary_Proband_998 (assumed male)
DiseaseAssertion: None (FIX:C: 18)
FamilyInfo: None
ParentalTesting: N/A
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
mutations
Case#: HB385
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity FIX:C: 2%
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
7
Case#: Enayat_Family 7
DiseaseAssertion: Severe Hemophilia B (Familial; from Shiraz, Iran)
FamilyInfo: Affected mothers and some sisters were investigated as the "family"
ParentalTesting:
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: < 0.01)
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
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
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
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
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
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
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
9-month old boy was diagnosed with severe haemophilia B
Case1: Male, 9-months at time of diagnosis
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0001933 (Subcutaneous hemorrhage), HP:0007420 (Spontaneous hematomas), HP:0012233 (Intramuscular hematoma), HP:0005261 (Joint hemorrhage)
CaseHPOFreeText: FIX: C <1%, recurrent anaphylactic reactions to FIX (abdominal pain, respiratory arrest, and severe hypotension)
CasePreviousTesting: F9 analysis (revealed a point mutation at exon H)
Gene: F9
Variant: NM_000133.3(F9):c.880C>T (p.Arg294Ter)
LegacyVariant: g 30863 C>T; Arg 248 stop
ClinVar: 10587 https://www.ncbi.nlm.nih.gov/clinvar/variation/10587/
gnomAD: Not reported
060–2010
Case#: 060-2010
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1834C>T
LegacyVariant:
ClinVar: No
CAID: CA255129
gnomAD:
g.6365G>A
Case#: Awidi_Variant_1 (9 patients, 2 families)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: Positive family history
ParentalTesting: Positive family history
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
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
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
genetic defects
Case#: Lin_Patient 3 (assumed male, Chinese origin)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1 ; FIX:Ag: 38)
CaseNotHPOs: N/A
CasePreviousTesting: None
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
2
Case#: Quadros_Proband_ ID_#2
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.112A>C (p.Asn38His)
ClinVar: Absent
CAID: CA414435439
gnomAD: Absent/Not Reported
c.59T>Cp.Leu20Ser
Case#: Huang_Proband_2
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
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
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
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)
6365G>A (R-4Q)
Case#: Balraj_Proband (from Malaysia)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: None
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
LegacyVariant: 6365 G>A (p.Arg-4Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
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
mutation
Case#: Knobloch_Malmo_20 (assumed male, German)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
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: c.6364C>T (p.Arg-4Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
mutations
Case#: Chan_Hong Kong 2 & Chan_Hong Kong 3 (Southern Chinese, assumed male)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: Carrier testing of at risk females in each family was completed by direct restriction enzyme analysis after determination of the specific FIX defect for the index patient
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (Chan_Hong Kong 2 FIX:Ag: 0.93; FIX:C: 0.04) (Chan_Hong Kong 3 FIXAg: 0.82; FIX:C: 0.01)
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
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
missense mutation
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)
mutations
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
3-year-old boy
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
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