6
Case#: 6, male, 22 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1063C>T
LegacyVariant:
ClinVar: 10139
CAID: CA255031
gnomAD:
41
Case#: 41, male, 20 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.881C>T
LegacyVariant:
ClinVar: 10190
CAID: CA255077
gnomAD:
111
Case#: 111, male, 31 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.144-2A>G
LegacyVariant:
ClinVar: No
CAID: CA414920419
gnomAD:
39
Case#: 39, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.677G>A
LegacyVariant:
ClinVar: No
CAID: CA414919166
gnomAD:
107
Case#: 107, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 9.3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6814A>C
LegacyVariant:
ClinVar: No
CAID: CA414903910
gnomAD:
174
Case#: 174, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons1_26
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
93
Case#: 93, male, 45 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 18%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6444T>A
LegacyVariant:
ClinVar: No
CAID: CA414907970
gnomAD:
165
Case#: 165, male, 28 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.4339delG
LegacyVariant:
ClinVar: No
CAID: CA873341376
gnomAD:
122
Case#: 122, male, 33 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6115+1G>C
LegacyVariant:
ClinVar: No
CAID: CA414904456
gnomAD:
170
Case#: 170, male, 42 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6876_6877delCT
LegacyVariant:
ClinVar: No
CAID: CA873368227
gnomAD:
100
Case#: 100, male, 15 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6551A>C
LegacyVariant:
ClinVar: No
CAID: CA414907026
gnomAD:
29
Case#: 29, male, 21 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2.3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.337C>T
LegacyVariant:
ClinVar: No
CAID: CA414919977
gnomAD:
74
Case#: 74, male, 60 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 11%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5545T>A
LegacyVariant:
ClinVar: No
CAID: CA414908552
gnomAD:
87
Case#: 87, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.9%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6406G>A
LegacyVariant:
ClinVar: No
CAID: CA414899430
gnomAD:
120
Case#: 120, male, 51 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5220-2A>G
LegacyVariant:
ClinVar: No
CAID: CA414911437
gnomAD:
60
Case#: 60, male, 19 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2029T>C
LegacyVariant:
ClinVar: 10244
CAID: CA255136
gnomAD:
104
Case#: 104, male, 13 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6683G>A
LegacyVariant:
ClinVar: 10098
CAID: CA255016
gnomAD:
138
Case#: 138, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.dup exons23_25
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
79
Case#: 79, male, 8 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5594A>G
LegacyVariant:
ClinVar: No
CAID: CA414908275
gnomAD:
2
Case#: 2, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.98G>A
LegacyVariant:
ClinVar: No
CAID: CA414920533
gnomAD:
182
Case#: 182, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons15_26
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
12
Case#: 12, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1798G>T
LegacyVariant:
ClinVar: No
CAID: CA414911019
gnomAD:
9
Case#: 9, male, 19 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1285C>T
LegacyVariant:
ClinVar: No
CAID: CA414915370
gnomAD:
114
Case#: 114, male, 16 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.601+1G>C
LegacyVariant:
ClinVar: No
CAID: CA414919361
gnomAD:
5
Case#: 5, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.741G>A
LegacyVariant:
ClinVar: No
CAID: CA414919022
gnomAD:
64
Case#: 64, male, 6 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2158G>C
LegacyVariant:
ClinVar: No
CAID: CA414903786
gnomAD:
23
Case#: 23, male, 21 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6496C>T
LegacyVariant:
ClinVar: 10096
CAID: CA255013
gnomAD:
99
Case#: 99, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6544C>T
LegacyVariant:
ClinVar: 10321
CAID: CA255214
gnomAD:
92
Case#: 92, male, 61 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 4.2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6440G>T
LegacyVariant:
ClinVar: No
CAID: CA414908004
gnomAD:
106
Case#: 106, male, 12 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6683G>A
LegacyVariant:
ClinVar: 10098
CAID: CA255016
gnomAD:
54
Case#: 54, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 17%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1834C>T
LegacyVariant:
ClinVar: 10236
CAID: CA255129
gnomAD:
Twenty-five novel mutations of the factor IX gene in haemophilia B
PMID: 8680410
Gene: F9
HGNC: 3551
Germline origins in the human F9 gene: frequent G:C→A:T mosaicism and increased mutations with advanced maternal age
PMID: 10647899
Gene: F9
HGNC: 3551
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
047–1004
Case#: 047-1004
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
080–2002
Case#: 080-2002
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.1649G>A
LegacyVariant:
ClinVar: No
CAID: CA255115
gnomAD:
048–1002
Case#: 048-1002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
038–2002
Case#: 038-2002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.5687_5690delCT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
016–2001
Case#: 016-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.901C>T
LegacyVariant:
ClinVar: No
CAID: CA414917990
gnomAD:
003–2005
Case#: 003-2005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.5275delG
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
071–2007
Case#: 071-2007
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.1208A>C
LegacyVariant:
ClinVar: No
CAID: CA414916134
gnomAD:
060–2009
Case#: 060-2009
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:
016–2003
Case#: 016-2003
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.2129G>A
LegacyVariant:
ClinVar: No
CAID: CA414904142
gnomAD:
020–1011
Case#: 020-1011
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
004–2017
Case#: 004-2017
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
091–2004
Case#: 091-2004
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
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.5281T>C
LegacyVariant:
ClinVar: No
CAID: CA414911024
gnomAD:
038–2025
Case#: 038-2025
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.514T>G
LegacyVariant:
ClinVar: No
CAID: CA414919550
gnomAD:
016–2005
Case#: 016-2005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.3531_3533delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
004–2008
Case#: 004-2008
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.4379dupA
LegacyVariant:
ClinVar: No
CAID: CA645292749
gnomAD:
035–2021
Case#: 035-2021
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.5954G>A
LegacyVariant:
ClinVar: No
CAID: CA414905715
gnomAD:
035–1005
Case#: 035-1005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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.1271þ1G>C
LegacyVariant:
ClinVar: No
CAID: CA414915615
gnomAD:
038–2011
Case#: 038-2011
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.5252A>G
LegacyVariant:
ClinVar: No
CAID: CA414911251
gnomAD:
020–2057
Case#: 020-2057
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
035–2019
Case#: 035-2019
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.923C>T
LegacyVariant:
ClinVar: No
CAID: CA255082
gnomAD:
035–2001
Case#: 035-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.1963_1964insT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
071–2027
Case#: 071-2027
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.4184_4186delGGAinsCCTC
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
020–1016
Case#: 020-1016
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
015–2006
Case#: 015-2006
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.343G>T
LegacyVariant:
ClinVar: No
CAID: CA414919965
gnomAD:
060–2001
Case#: 060-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
066–2003
Case#: 066-2003
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.1649G>A
LegacyVariant:
ClinVar: No
CAID: CA255115
gnomAD:
010–1001
Case#: 010-1001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
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.6742T>A
LegacyVariant:
ClinVar: No
CAID: CA414904758
gnomAD:
002–2002
Case#: 002-2002
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
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.2092T>C
LegacyVariant:
ClinVar: No
CAID: CA414908999
gnomAD:
038–2023
Case#: 038-2023
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.322_332þ8delGCTTCTGAGGGtgagtaaa
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
002–2006
Case#: 002-2006
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.4379delA
LegacyVariant:
ClinVar: No
CAID: CA255151
gnomAD:
001–2040
Case#: 001-2040
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
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.5630G>A
LegacyVariant:
ClinVar: No
CAID: CA414908131
gnomAD:
003–2001
Case#: 003-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
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.493C>T
LegacyVariant:
ClinVar: No
CAID: CA255065
gnomAD:
37-year old woman
Case1: Female patient, 37-year-old, At age 25(pregnant) an F8 mutation was identified, Family History of Severe HA
DiseaseAssertion: Mild hemophilia A due to a family mutation and de novo mutation
FamilyInfo: Family also has the large deletion of exon 1 to 22 of the F8 gene, Son (age 10) has mild Hemophilia A
ParentalTesting: Father tested negative for any F8 mutations, Mother is an asymptomatic carrier of the familial large deletion
CasePresentingHPOs: HP:0000978 (Bruising Susceptibility), HP:0000132 (Menorrhagia)
CaseHPOFreeText: FVIII:C 7%, compounded heterozygous for the large gene deletion and c.1569G>T mild mutation
CasePreviousTesting: Molecular analysis, Sequenced the whole coding region of the F8 gene
Gene: F8
Variant: 1. F8, EX1-22DEL 2. NM_000132.3:c.1569G>T (p.Leu523=)
ClinVar: 1. 10122 https://www.ncbi.nlm.nih.gov/clinvar/variation/10122/
gnomAD: 1. Not reported (F8, EX1-22DEL)
a woman diagnosed as a HA carrier
Case2: Female patient, blood group O
DiseaseAssertion: Severe Hemophilia A from de novo mutation
FamilyInfo: Family history of severe Hemophilia A, Son diagnosed with severe HA, Sibling has intron 22 inversion on F8 gene
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeRext: aPTT ratio 1.16 (within normal range ratio), FVIII:C 48% (low-normal)
CasePreviousTesting: Molecular analysis that excluded intron 22 inversion (HA carrier), tested for intron 22 inversion (confirmed negative), tested for intron 1 inversion (found negative), sequenced the whole coding region of the F8 gene(c.1753-1G>A mutation found)
Gene: F8
Variant: NM_000132.3:c.1753-1G>A
ClinVar: NA
CAID: CA414911340
gnomAD: 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
IVS13 a-2g
Case#: 10
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Inhibitors present
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.2114-2A>G
ClinVar: NA
CAID: CA414904364
gnomAD: NA
c.1421G>T
Case#: 19
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.1421G>T (p.Gly455Val)
ClinVar: NA
CAID: CA414914381
gnomAD: Not reported
Table 2
Case#: Cz1, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
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:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
Table 2
Case#: Cz33, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 8%
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:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
Table 1
Case#: Cz12, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
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
Table 1
Case#: Cz31, 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:c.1324T>C (p.Tyr442His)
ClinVar: NA
CAID: CA414915029
gnomAD: Not reported
Table 2
Case#: Cz11, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
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:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
Table 2
Case#: Cz26, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 1.5%
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:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
Table 1
Case#: Cz37, 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:c.4379dup (p.Asn1460LysfsTer2)
ClinVar: NA
CAID: CA645292749
gnomAD: MAF for p.Asn1460LysfsTer2 in the European (non-Finnish) population 0.00001245<br>https://gnomad.broadinstitute.org/variant/X-154157685-A-AT
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:
S29
Case#: S29, Iranian
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 30%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.2110C>T
LegacyVariant:
ClinVar: No
CAID: CA10568366
gnomAD:
S26
Case#: S26, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.3943delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
S23
Case#: S23, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
S5
Case#: S5, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.1010‐2A>G
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
S15
Case#: S15, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Family history of HA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
S12
Case#: S12, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Family history of HA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.del exons8_9
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
S19
Case#: S19, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
mutation
No mention of NM_000133.4:c.128G>A (p.Arg43Gln) in this paper.
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
mutation
No Case Level Evidence for NM_000133.4:c.128G>T (p.Arg43Leu)
Mutations Causing Hemophilia B: Direct Estimate of theUnderlying Rates of Spontaneous Germ-Line Transitions,Transversions, and Deletions in a Human Gene
PMID: 2198809
Gene: F9
HGNC: 3551
Factor IX San Dimas
PMID: 2738071
Gene: F9
HGNC: 3551**
Toward Understanding the Antitumor Effects of Water-Soluble Fullerene Derivatives on Lung Cancer Cells: Apoptosis or Autophagy Pathways?
PMID: 31361134
Gene: F8
No Evidence: This article does not mention F8 or Hemophilia A.
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.6113A>G
Case#: 28
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 5/3% (Moderate Phenotype), No inhibitors present
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: F8
Variant: NM_000132.3(F8):c.6113A>G (p.Asn2038Ser)
ClinVar: 10305 https://www.ncbi.nlm.nih.gov/clinvar/variation/10305/
CAID: CA255198
gnomAD: Not reported
IVS22
Case#: 30
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1%, Severe Phenotype, Inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, possibility that sample was blinded for NGS and validated by comparing results with Sanger Sequencing
Gene: F8
Variant: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/#id_second
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.1648C>T
Case#: 13
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 25/21% (Mild Phenotype), No inhibitors present
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: F8
Variant: NM_000132.3(F8):c.1648C>T (p.Arg550Cys)
ClinVar: 10223 https://www.ncbi.nlm.nih.gov/clinvar/variation/10223/
CAID: CA255113
gnomAD: Not reported
c.5999–740T>C
Case#: 26
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 33%, Mild Phenotype, No inhibitors present
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: F8
Variant: NM_000132.3:c.5999-740T>C
ClinVar: NA
CAID: CA1139532039
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.6046C>T
Case#: 27
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 4% (Moderate Phenotype), No inhibitors present
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: F8
Variant: NM_000132.3(F8):c.6046C>T (p.Arg2016Trp)
ClinVar: 10304 https://www.ncbi.nlm.nih.gov/clinvar/variation/10304/
CAID: CA255197
gnomAD: Not reported
c.6750A>C
Case#: 35
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 24/32/19/17/35%, Mild Phenotype, No inhibitors present
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: F8
Variant: NM_000132.3:c.6750A>C (p.Gln2250His)
ClinVar: NA
CAID: CA414904711
gnomAD: Not reported
c.5936G>A
Case#: 25
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 21/17%, Mild Phenotype, No inhibitors present
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: F8
Variant: NM_000132.3:c.5936G>A (p.Gly1979Glu)
ClinVar: NA
CAID: CA414905839
gnomAD: Not reported
c.157G>A
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.157G>A (p.Glu53Lys)
ClinVar: NA
CAID: CA414435726
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.6506G>A
Case#: 31
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 17/25%, Mild Phenotype, inhibitors present
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: F8
Variant: NM_000132.3(F8):c.6506G>A (p.Arg2169His)
ClinVar: 10315 https://www.ncbi.nlm.nih.gov/clinvar/variation/10315/
CAID: CA255208
gnomAD: Not reported
c.1010–842G>A
Case#: 7
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 34/30/35% (Mild Phenotype), No inhibitors present
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: F8
Variant: NM_000132.3:c.1010-842G>A
ClinVar: NA
CAID: CA337336857
gnomAD: MAF in Ashkenazi Jewish population 0.01105<br>https://gnomad.broadinstitute.org/variant/X-154195804-C-T
B1 – B13
Case#: B1 - B13
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 17, FVIII:AG = 18, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.940A>G
LegacyVariant:
ClinVar: No
CAID: CA255084
gnomAD:
B30. B31
Case#: B30, B31
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 6, FVIII:AG = 10, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.2161A>C, NM_000132.4:c.2161A>T
LegacyVariant:
ClinVar: No
CAID: CA414903738, CA414903741
gnomAD:
B73
Case#: B73
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 41, FVIII:AG = 113, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.5123G>A
LegacyVariant:
ClinVar: No
CAID: CA255154
gnomAD:
A1
Case#: A1
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 7, FVIII:AG = 25, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.398A>G
LegacyVariant:
ClinVar: No
CAID: CA255061
gnomAD:
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
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)
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
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:
A genetic analysis of 23 Chinese patients with hemophilia B
PMID: 27109384
Gene: F9
HGNCID: 3551
The molecular basis of hemophilia BEdyta Odnoczko , Daria Malarczyk , Agata Adamiec
PMID: No PMID (chrome-extension://bjfhmglciegochdpefhhlphglcehbmek/pdfjs/web/viewer.html?file=https%3A%2F%2Filliad.lib.unc.edu%2FNOH%2Filliad.dll%3FAction%3D10%26Form%3D75%26Value%3D3078221)
Gene: F9
HGNC: 3551
Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B
PMID: 10739381
Gene: F9
HGNC: 3551
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
.A37D
Only mention of NM_000133.4:c.110C>A (p.Ala37Asp) in this publication.
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
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
Clinical assessment of cervical movement sense in those with neck pain compared to asymptomatic individuals
PMID: 31277033
Gene: F8
NoEvidence: This article does not discuss Hemophilia A, F8 or blood disorders.
A Mutation in the Propeptide of Factor IX Leads to WarfarinSensitivity by a Novel Mechanism
PMID: 8833911
Gene: F9
HGNC: 3551
UQU-HB10
Case#: UQU-HB10, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, Unable to flex knees fully, PTT 45.8
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
UQU-HB12
Case#: UQU-HB12, Male, 12-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, Unable to flex knees fully, PTT 73.1
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
UQU-HA37
Case#: UQU-HA37, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 49.6, FVIII: 1 to <5% (Moderate), Disabled left knee
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.6430-1G>A
ClinVar: NA
CAID: CA414908097
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
Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies
PMID: 28270892
Gene: F8, F9
HGNCID: 3546, 3551
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
UQU-HA34
Case#: UQU-HA34, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 94, Disabled Left elbow, 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.1835G>C (p.Arg612Pro)
ClinVar: NA
CAID: CA414910775
gnomAD: Not reported
mutations
The only mention of NM_000133.4:c.135G>T (p.Lys45Asn) in this publication was in reference to other publications that have case level data on this specific variant.
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
FACTOR IX MUTATIONS: RAPID, DIRECT SCREENING METHODS FOR 20 NEWFAMILIESWITHHEMOPHILIAB
PMID: 1579901
Gene: F9
HGNC: 3551
Advances and challenges for hemophilia gene therapy
PMID: 31332444
Gene: F8
InsufficientEvidence: Patients are mentioned; however, no mention of variants.
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
PMID: 8318985
Gene: F9
HGNC: 3551
.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
, similarly to other HB-related changes(p.Cys28Arg/Gly/Tyr)
No case level data for NM_000133.4:c.82T>C (p.Cys28Arg) in this paper.
16-year-old boy
Case1: Male patient, 16-year-old, Tabriz Iran
DiseaseAssertion: Moderate Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0005261 (Joint hemorrhage), HP:0030137 (Prolonged bleeding following circumcision)
CasePreviousTesting: PCR-SSCP and PCR-CSGE was performed for all 26 exons with exon-intron boundaries of F8. Abnormal PCR product were directly sequenced.
Gene: F8
Variant: NM_000132.3(F8):c.4925A>G (p.Glu1642Gly)
ClinVar: NA
CAID: CA10568060
gnomAD: MAF for Glu1642Gly in the East Asian population 0.0001346 <br /> https://gnomad.broadinstitute.org/variant/X-154157140-T-C
Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians
PMID: 8499919
Gene: F9
HGNC: 3551
For p.Val682Leu,
Case#: P5 (female)
DiseaseAssertion: Carrier
FamilyInfo: N/A
ParentalTesting: Investigation found that large gene defect was not found in the patient P5's mother and grandmother
CasePresentingHPOs: HP:0003125, HP:0001928, HP:0001892
CaseHPOFreeText: Low FVIII levels (FVIII:C levels were significantly decreased compared to the WT (13.4% ± 0.8, P < 0.01); FVIII:Ag levels were normal both in the conditioned media and cell lysate (respectively 90.7% ± 6.3 and 109.0% ± 9.5)), abnormal blood coagulation, mild bleeding tendency, haematoma
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.
Gene: F8
Variant: NM_000132.4:c.2044G>C
CAID: CA414909252
gnomAD: Absent/Not Reported
Usefulness of an in vitro cellular expression model for haemophilia A carrier diagnosis: illustration with five novel mutations in the F8 gene in women with isolated factor VIII:C deficiency
PMID: 25708597
Gene: F8
Disease: Hemophilia A
HGNC:3546
MONDO ID: MONDO:0010602
Novel approach to genetic analysis and results in 3000 hemophilia patients enrolled in the My Life, Our Future initiative
PMID: 29296726
Gene: F9
HGNC: 3551
Click here for additional data file.(2
NM_000133.4:c.128G>A (p.Arg43Gln) is mentioned in the paper, however, there is no case level data associated with the mentioned variant.
The patient was born in 1944; at the age of 7 he underwent a tonsillectomy, bled excessively and required a blood transfusion. He had dental extractions when he was 14 and bled for a week afterwards. At 25 he had a birthmark removed from his left shoulder and again bled excessively. At that time two-stage FVIII:C assays were performed and he was diagnosed as having mild haemophilia A with a FVIII:C level of 19%. 3 years later (in 1972) he presented with a large haematoma of the buttock after minor trauma and a two-stage assay reported a FVIII:C level of 11%. Interestingly, his APTT was always normal. In 1977 he had sebaceous cysts removed under the cover of FVIII concentrate. He received further concentrate in 1982 following an injury to his left thigh and 6 weeks later developed hepatitis (in retrospect hepatitis C). He has not had any further bleeding problems. At a recent routine visit his baseline FVIII:C level was checked with our (now routine) one-stage assay and found to be normal. Subsequently on three blood samples taken on different days we obtained the assay results shown in Table I. On the second of these samples the factor VIII antigen was measured by Immunozym ELISA (Techniclone, Dorking) and found to be 82 iu/dl.
Case#: 77 year old male*
DiseaseAssertion:Hemophilia A, mild
FamilyInfo: Brother does not have hemophilia
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The factor VIII coding region was amplified into six overlapping segments from traces of mRNA and from genomic DNA and subsequently sequenced
Gene: F8
Variant: NM_000132.3:c.5918A>T
LegacyVariant:
ClinVar:
CAID: CA414905984
gnomAD:
Spectrum of F8 Genotype and Genetic Impact on Inhibitor Development in Patients with Hemophilia A from Multicenter Cohort Studies (J-HIS) in Japan
PMID: 33254277
Gene: F8
HGNCID: 3546
heterozygous hemophilia A in a female patient
PMID:24317041
Gene:F8
HGNC ID:3546
Compound heterozygous hemophilia A in a female patient and the identification of a novel missense mutation, p.Met1093Ile
PMID: 24317041
Gene: F8
HGNCID: 3546
Table 1.
No evidence of NM_000133.4:c.84T>G (p.Cys28Trp) in this paper.
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
Molecular analysis of hemophilia B in Poland: 12 novel muta-tions of the factor IX gene®
NM_000133.4(F9):c.19A>T (p.Ile7Phe) is not reported in this paper.
(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
Role of chromogenic assays in haemophilia A and B diagnosis
PMID: 29808946
Gene: F8
HGNC: 3546
NoEvidence: This article discusses the role of chromogenic assays in hemophilia A; no case reports in this article
Importance of diagnostic guidance in acquired hemophilia A
PMID: 31344171
Gene: F8
No Evidence: No variants or probands mentioned in this review of Hemophilia A
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
Missense mutations at ALA-10 in the factor IX propeptide:an insignificant variant in normal life but a decisive causeof bleeding during oral anticoagulant therapy
PMID: 9233593
Gene: F9
HGNC: 3551
Extensive serum cytokine analysis in patients with prostate cancer
PMID: 31430659
Gene: F8
No Evidence: This article does not mention F8, rather it discusses cytokine analysis.
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
variants
No mention of NM_000133.4:c.138G>T (p.Arg46Ser) in this publication.
Defective Propeptide Processing of BloodClotting Factor IX Caused by Mutation ofArginine to Glutamine at Position -
PMID: 3009023
Gene: F9
HGNC: 3551
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
Enhanced potency of recombinant factor VIIa with increased
PMID: 31549480
Gene: F8
InsufficientEvidence: This article mentions variants and patient tissue being used separately; however, does not tie them in together, without a variant to tie the proband to, it’s insufficient evidence
c.138GNT
A case of NM_000133.4:c.138G>T (p.Arg46Ser) is mentioned in this paper, but previously reported, and no case level evidence is given in this publication.
.A37D
Only mention of NM_000133.4:c.110C>A (p.Ala37Asp) in this publication.
mutations
Case#: VAN DE Water_NZ 2 (New Zealand, assumed male)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: In 22 of the 32 families the mutation resulted in alteration of a restriction enzyme site. In these cases, researchers developed a rapid PCR based diagnosis assay, which eliminated the need for extensive family studies (enabled successful prenatal and carrier diagnostic studies to be undertaken in 22 subjects from five families)
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (2%)
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
LegacyVariant: c.6365 G>A (p.Arg-4Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
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
Prediction of factor VIII inhibitor development in the SIPPET cohort by mutational analysis and factor VIII antigen measurement
PMID: 29399993
Gene: F8
HGNC: 3546
InsufficientEvidence: This article mentions variants however there are no specific case reports mentioned therefore, insufficient evidence
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
Homozygous and heterozygous retinal phenotypes in families harbouring IMPG2 mutations
PMID: 31264916
Gene: IMPG2
HGNC: 18362
Disease: retinitis pigmentosa 56
MONDO: 0013314
InheritancePattern: semi-dominant
Prevalence: Vitelliform macular dystrophy in general is estimated to have a prevalence of 1 in 5,500 (PMID: 27120116).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete, while heterozygous carriers of deleterious variants show incomplete penetrance and variable expressivity.
We demonstrate that in CLN5-depleted HeLa cells, the lysosomal sorting receptors sortilin and cation-independent mannose 6-phosphate receptor (CI-MPR) are degraded in lysosomes due to a defect in recruitment of the retromer (an endosome-to-Golgi compartment trafficking component).
ExperimentName: Defective lysosomal sorting receptor degradation in CLN5-depleted HeLa cells
NonPatientCell: HeLa cells (EFO:0001185)
GeneFunction: Lysosomal organization (GO:0007040)
GeneAlteration: CLN5 (or the CLN1 control) was depleted by transient transfection of small interfering RNA (siRNA) into HeLa cells, 48 hrs. before assays were performed.
FunctionalEvidence: CLN5-depleted cells have reduced immunofluorescent signal (Fig. 2K) and reduced expression (Fig. 3A) of two lysosomal sorting receptors; cation-independent mannose 6-phosphate receptor (CI-MPR) and sortilin (Fig. 2K). CLN5-depleted cells also have fragmented TGN46 signal (Fig. 2Q) and increased precursor and intermediate forms of the lysosomal cargo protein cathepsin D (Fig. 3C). These findings are consistent with CI-MPR and sortilin failing to correctly recycle to the Golgi and being degraded in lysosomes instead, possibly due to a defect in a complex called retromer, which returns membrane-associated proteins from the endosome to the Golgi or other cellular compartments. Endosomal signal for the retromer subunit Vps26 is also decreased (Fig. 4E), and both Vps26 and Vps35 are increasingly cytosolic rather than membrane-bound in CLN5-depleted cells (Fig. 6A). These defects are reversed by exogenously expressing CLN5 (Fig. 7B). Rab7 recruitment to the endosome is also defective in CLN5-depleted cells (Figs. 8B,8M). Considering that CLN5 interacts with Rab5 and Rab7 (Fig. 9A), it may serve as a scaffold recruiting Rab7 and the retromer complex to the endosomal membrane, for the purpose of recycling membrane-associated receptors such as sortilin and CI-MPR out of the endosome. Thus, patients with CLN5 loss-of-function variants may have defective recruitment of the retromer complex to the lysosome / endosome and disordered trafficking of membrane proteins out of these compartments as a result.
FAVariants: N/A
Rp1L1−/− mice display scattered OS disorganization, reduced electroretinogram amplitudes, and progressive photoreceptor degeneration, less severe and slower than in Rp1−/− mice. In single rods of Rp1L1−/−, photosensitivity is reduced, similar to that of Rp1−/−. While individual heterozygotes are normal
Six Novel Missense Mutations in the LDL Receptor-Related Protein 5 (LRP5) Gene in Different Conditions with an Increased Bone Density
PMID: 12579474
Gene: LRP5
HGNC: 6697
Disease: osteoporosis-pseudoglioma syndrome
MONDO: 0009820
InheritancePattern: autosomal recessive
Prevalence: osteoporosis-pseudoglioma syndrome is estimated to occur in 1 out of every 2,000,000 live births.
Penetrance: The penetrance of the phenotype among homozygous or compound heterozygous cases appears to be complete, while heterozygous carriers of deleterious variants appear to be mildly affected.
The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p
PMID: 9257651
Gene: PRPF4
HGNC: 17349
Disease: retinitis pigmentosa 70
MONDO: 0014400
InheritancePattern: autosomal dominant
Prevalence: The overall prevalence of retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,500 and 1 in 27,000). The proportion of that incidence made up by the specific form caused by variants in PRPF4 is not clear.
Penetrance: Known disease-causing alleles appear to be incompletely penetrant (PMID: 25383878).
Retinitis pigmentosa
Case#: Jespersgaard_2019_Patient_167, gender and age not specified, origin likely to be Danish based on cohort
CasePresentingHPOs: N/A
CaseHPOFreeText: The proband has been diagnosed with retinitis pigmentosa, as part of a larger group of generalized non-syndromic retinal dystrophies. Detailed phenotypes are not described.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease.
CaseMethod1: NGS panel
CaseMethod2: N/A
CaseGenotypingMethod: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease. It is not clear whether Sanger sequencing was used to validate the genotyping of this particular case.
Variant: The proband harbors the NM_000440.3(PDE6A):c.627+2T>G variant in the homozygous state.
ClinVar: 636057
gnomAD: The NM_000440.3(PDE6A):c.627+2T>G variant is not found in gnomAD v2.1.1.
VariantEvidence: The NM_000440.3(PDE6A):c.627+2T>G variant disrupts a canonical splice site in intron 2, but does not have experimental confirmation of exon skipping or frameshift.
CaseAddInfo: N/A
CasePMIDs: N/A
Retinitis Pigmentosa
Case#: Jespersgaard_2019_Patient_162, gender and age not specified, origin likely to be Danish based on cohort
CasePresentingHPOs: N/A
CaseHPOFreeText: The proband has been diagnosed with retinitis pigmentosa, as part of a larger group of generalized non-syndromic retinal dystrophies. Detailed phenotypes are not described.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease.
CaseMethod1: NGS panel
CaseMethod2: N/A
CaseGenotypingMethod: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease. It is not clear whether Sanger sequencing was used to validate the genotyping of this particular case.
Variant: The proband harbors the NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) variants in the compound heterozygous state.
ClinVar: 636052, 636051
gnomAD: The NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) variants are not found in gnomAD v2.1.1.
VariantEvidence: NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) are nonsense variants in exons 10 and 7, respectively. They are predicted to result in nonsense-mediated decay or at least to respectively truncate the C-terminal ~59% or ~50% of the protein product.
CaseAddInfo: N/A
CasePMIDs: N/A
In this study, we have generated and characterized Oa1-deficient mice by gene targeting (KO). The KO males are viable, fertile and phenotypically indistinguishable from the wild-type littermates. Ophthalmologic examination shows hypopigmentation of the ocular fundus in mutant animals compared with wild-type. Analysis of the retinofugal pathway reveals a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibres at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE shows the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells, suggests that the giant melanosomes may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.
ExperimentName: Mouse model with hemizygous disruption of the GPR143 ortholog Oa1
NonHumanModel: Mus musculus
GeneAlteration: A hemizygous mouse model of Oa1 knockout was generated by replacement of exon 1 (including the start codon) with a cassette to facilitate selection.
ModelPhenotype: HP:0007894 (Hypopigmentation of the fundus), HP:0025551 (Optic nerve misrouting), Giant melanosomes in retinal pigment epithelial cells
HumanPhenotype: HP:0000639 (Nystagmus), HP:0003593 (Infantile onset), HP:0007663 (Reduced visual acuity), HP:0001361 (Nystagmus-induced head nodding), HP:0000646 (Amblyopia), HP:0000483 (Astigmatism), HP:0000613 (Photophobia), normally pigmented skin and hair, HP:0005592 (Giant melanosomes in melanocytes), HP:0007750 (Hypoplasia of the fovea), HP:0007894 (Hypopigmentation of the fundus), HP:0025551 (Optic nerve misrouting)
ModelEvidence: Although the coat, eye color, and ERG responses of the mice were unaffected, the mice match the human patients in that they exhibit hypopigmentation of the fundus (Fig. 2), optic fiber misrouting at the chiasm, and expansion of individual melanosomes into giant melanosomes within cells of the RPE (Figures 2, 3). The mice match the mode of inheritance from the human patients.
ModelVariant: This model features disruption of Oa1 by knockout, but does not harbor a mutation equivalent to a variant from a human patient.
Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease
PMID: 28041643
GeneName: GNAT2
HGNC: 4394
Disease: achromatopsia 4
MonDO ID: MONDO_0013465
Inheritance: autosomal recessive
The significance of diminished IFT-A enrichment at the basal body is unclear. It may affect flagellar assembly kinetics because the mutant cells may not be able to readily utilize large quantities of IFT-A from the flagellar base during flagellar assembly. To test this, ift43Δ136 and ift140 mutants were deflagellated to allow flagellar regeneration. Consistent with a previous report [38], wild type cells and the mutant ift43Δ113 with an intact IFT43 conserved domain rapidly regenerated full length flagella (Fig 6A). The ift43Δ136 and ift140mutant cells could regenerate flagella to their original length but at a slower rate especially in theift140 mutant. Thus, the availability of the proper amount of IFT-A at the flagellar base may play a role in determining the rate of flagellar assembly.
ExperimentName: Chlamydomonas mutant model of IFT140 loss-of-function
NonHumanModel: Chlamydomonas reinhardtii
GeneAlteration: The Ift140 mutant model has disruption of the Chlamydomonas gene by insertion of the paromomycin resistance gene AphVIII between bases 8234 and 8235 of the IFT140 gene (in exon 21 of 28).
ModelPhenotype: The mutant exhibits short flagella due to slower flagellar regeneration as well as absence of IFT43 and IFT122 (IFT-A proteins) from the peri-basal body (shown by immunofluorescent co-localization with α-tubulin).
HumanPhenotype: The human patients exhibit the absence of cilia from fibroblasts
ModelEvidence: The cellular defects of the model in flagellar regeneration/assembly (Figures 6A,6C) parallel the absence of cilia from a high proportion of patient fibroblasts. The model also helps explain this defect by showing the underlying cause; the absence of IFT-A complex components from the peri-basal body region (Figure 5E-5F).
ModelVariant: The model does not feature any of the variants observed in human patients.
mutations
Case#: Holmberg_Patient_6, male, age 2 at onset and age 13 at death, Dutch origin
CasePresentingHPOs: HP:0003208 (Fingerprint intracellular accumulation of autofluorescent lipopigment storage material), HP:0011463 (Childhood onset), HP:0001268 (Mental deterioration), HP:0000572 (Visual loss), HP:0001251 (Ataxia), HP:0011421 (Death in adolescence), HP:0002540 (Inability to walk), HP:0001250 (Seizure), HP:0000550 (Undetectable electroretinogram), HP:0012018 (EEG with temporal focal spikes), HP:0100952 (Enlarged sylvian cistern), HP:0006855 (Cerebellar vermis atrophy), HP:0002198 (Dilated fourth ventricle), HP:0033725 (Thin corpus callosum), HP:0030891 (Periventricular white matter hyperdensities), HP:0012690 (T2 hypointense thalamus)
CaseHPOFreeText: This patient exhibited the most rapid clinical course from the group of 8 patients. Age of onset was 2, while mental decline was present at age 3 and visual deterioration at age 5. Ataxia, seizures, and abolished electroretinogram were found at age 7. Loss of independent walking occurred at age 8. Posterior EEG spikes in response to low-frequency photic stimuli were observed. T2-weighted images showed increased signal intensity of the periventricular white matter and posterior limb of the capsula interna. The thalamus had abnormally low signal intensity compared to the putamen, caudate nuclei, and white matter.
CaseNotHPOs: HP:0001312 (Giant somatosensory evoked potentials)
CaseNotHPOFreeText: Flash visual evoked potential (fVEP) was found to be normal at age 7.
CasePreviousTesting: Other than clinical phenotype characterization, it is not clear what genotype tests preceded CLN5 sequencing.
CaseMethod1: N/A
CaseMethod2: N/A
CaseGenotypingMethod: Each exon of CLN5 was PCR-amplified and Sanger sequenced in both directions.
Variant: The patient is homozygous for the NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) variant.
ClinVar: 2566 (homozygous)
gnomAD: The maximum allele frequency of the NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) variant is 0.00005437 (within the East Asian population, with no homozygous occurrences). https://gnomad.broadinstitute.org/variant/13-77574715-G-A
VariantEvidence: NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) is a recurring missense variant that has been previously shown to introduce an additional N-glycosylation site within the C-terminal region of CLN5 (PMID:20052765) and to disturb its localization to the lysosome (PMID:20052765).
CaseAddInfo: N/A
CasePMIDs: N/A
We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin. Subsequently, both cone and rod photoreceptors degenerate. RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability.
ExperimentName: Mouse knockout model of Rpgr loss-of-function
NonHumanModel: Mus musculus
GeneAlteration: The model has targeted hemizygous (male) or biallelic (female) disruption of the mouse Rpgr gene by insertion of a neomycin resistance cassette to replace exons 4 through 6 with a resistance cassette and generate a null variant.
ModelPhenotype: HP:0030612 (Abnormal retinal morphology on macular OCT), partial mislocalization of blue and green cone opsins to the inner segment, reduced rhodopsin content in the outer segment, HP:0000546 (Retinal degeneration), HP:0030609 (Photoreceptor layer loss on macular OCT), HP:0030610 (Photoreceptor outer segment loss on macular OCT), disorganization of disk membranes, normal connecting cilia morphology, HP:0030483 (Reduced amplitude of dark-adapted bright flash electroretinogram a-wave), HP:0008275 (Abnormal light-adapted electroretinogram),
HumanPhenotype: HP:0007642 (Congenital stationary night blindness), HP:0007994 (Peripheral visual field loss), HP:0000529 (Progressive visual loss), HP:0000365 (Hearing impairment), HP:0002205 (Recurrent respiratory infections), HP:0011109 (Chronic sinusitis), HP:0000388 (Otitis media), HP:0002837 (Recurrent bronchitis), HP:0012263 (Immotile cilia), HP:0005938 (Abnormal respiratory motile cilium morphology)
ModelEvidence: The model has been well-characterized at the ocular level and triggers molecular and photoreceptor cell defects (Figures 4a, 4b, 5, 6, 7a, and 7b) that are consistent with human patient features such as night blindness, central visual field loss, and peripheral visual field loss.
ModelVariant: The model does not feature a variant equivalent to one observed in human patients.
P09 GC29680 c.3399T>G p.Tyr1133* Homozygous
Case#: Georgiou_2024_Family_GC29680_Proband_P09, female, reported at age 30 years, family origin reported as from Bangladesh
CasePresentingHPOs: HP:0011003 (High myopia), HP:0030558 (Best corrected visual acuity 0.5 LogMAR)
CaseHPOFreeText: BCVA began at 0.39 logMAR and progressed to 0.54 logMAR.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous genotyping was by either next-generation sequencing panel, whole exome sequencing, or whole genome sequencing, but was unspecified.
CaseMethod1: NGS panel / WES / WGS
CaseMethod2: Sanger sequencing of RBP3
CaseGenotypingMethod: Previous genotyping by either next-generation sequencing panel, whole exome sequencing, or whole genome sequencing was followed by Sanger sequencing of RBP3.
Variant: The individual harbors the NM_002900.3(RBP3):c.3399T>G (p.Tyr1133Ter) variant in the homozygous state.
ClinVar ID: 3675731
gnomAD: The variant is found in gnomAD version 4.1.1 at a frequency of 0.00001098 (1 / 91070) in the South Asian population https://gnomad.broadinstitute.org/variant/chr10-47357112-T-G?dataset=gnomad_r4
VariantEvidence: NM_002900.3(RBP3):c.3399T>G (p.Tyr1133Ter) is a nonsense variant within exon 4 of 4 that is predicted to trigger nonsense-mediated decay.
CaseAddInfo: Potential consanguinity within the proband's family has not been commented on.
CasePMIDs: N/A
Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation
PMID: 30628748
Gene: RPE65
HGNC: 10294
Disease: Retinitis pigmentosa 87 with choroidal involvement
MONDO: 0032873
InheritancePattern: Autosomal Dominant
Prevalence: The overall prevalence of Retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of Retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,000 and 1 in 27,000). The prevalence of Retinitis pigmentosa 87 with choroidal involvement is considered to be much lower.
Penetrance: Incomplete penetrance, estimated at 80%
A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy.
Case#: Wells_1993_Proband_III/5, female, age 44 years at time of first examination, family origin not reported
CasePresentingHPOs: Adult onset HP:0003581, Visual impairment HP:0000505, Subretinal deposits HP:0031528, Abnormal light-adapted single flash electroretinogram HP:0030472.
CaseHPOFreeText: The proband has been diagnosed with adult vitelliform macular dystrophy, with onset in the mid-thirties. Foveal deposits are small, yellow, and at the RPE level.
CaseNotHPOs: Abnormal light-adapted flicker electroretinogram HP:0030473
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing consisted of screening of the RHO locus for disease-causing variants.
CaseMethod1: Sanger sequencing of PRPH2
CaseMethod2: N/A
CaseGenotypingMethod: Previous testing of this family consisted of screening of the RHO locus for variants causing RP, with negative results. Genotyping was performed by Sanger sequencing of the PCRs product to identify the variant.
Variant: The proband harbors the NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) variant in the heterozygous state.
ClinVar ID: 98707
gnomAD: The NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) variant was not found in gnomAD v4.0.0.
VariantEvidence: NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) is a nonsense variant in exon 2 of 3 that is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 26% of the protein product.
CaseAddInfo: Although the proband is the only family member genotyped and examined by the authors, her father was confirmed to be similarly affected. Family consanguinity was not reported.
CasePMIDs: N/A
deletion
Case#: Xin_Patient_9, sex not mentioned, age 6 at onset, U.S. nationality, Egyptian ethnicity
CasePresentingHPOs: HP:0004302 (Functional motor deficit), HP:0000572 (Visual loss), HP:0001250 (Seizure), HP:0001268 (Mental deterioration), HP:0011463 (Childhood onset), HP:0003736 (Autophagic vacuoles)
CaseHPOFreeText: Motor difficulty was the phenotype at presentation (age 6). Cognitive regression, Seizures, and Visual loss had onset at age 7. EM finding of vacuoles was made specifically in muscle.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing for mutations in the CLN1, CLN2, CLN3, CLN6, and CLN8 had already occurred, using PCR amplification and Sanger sequencing to exclude the possibility of variants in the exons and surrounding noncoding regions. Genome-wide analysis methods were not used, as NCL had already been diagnosed based on clinical phenotypes.
CaseMethod1: PCR amplification of the coding and surrounding non-coding regions of each gene, followed by bidirectional Sanger sequencing
CaseMethod2: as mentioned
CaseGenotypingMethod: CLN5 genotyping was performed by PCR amplification of the four exons and surrounding non-coding regions was performed, followed by bi-directional Sanger sequencing. Synthetic multiplex ligation-dependent probe amplification (MLPA) was then used to calculate average gene dosage ratio for each ratio, in order to detect large deletions.
Variant: The patient is believed to be homozygous for the NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 variant.
ClinVar: 56546 (homozygous)
gnomAD: The NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 variant is absent from gnomAD.
VariantEvidence: NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 is a frameshift variant that disrupts ~28% of the protein product.
CaseAddInfo: Parents have not been subjected to genotyping, so homozygosity of variants is assumed. This conclusion was supported by failure to detect a deletion, and by family history of consanguinity.
CasePMIDs: N/A