c.835G>A
Case#: 47
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 18/26% (Mild Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3(F9):c.835G>A (p.Ala279Thr)
ClinVar: 216926 https://www.ncbi.nlm.nih.gov/clinvar/variation/216926/
CAID: CA277507
gnomAD: Not reported
c.541G>A
Case#: 4
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 3/5/3% (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.541G>A (p.Val181Met)
ClinVar: 10177 https://www.ncbi.nlm.nih.gov/clinvar/variation/10177/
CAID: CA255066
gnomAD: Not reported
c.5374–19delT
Case#: 22, Female HA carrier
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 60%, 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.5374-19del
ClinVar: 439679 https://www.ncbi.nlm.nih.gov/clinvar/variation/439679/
CAID: CA10567985
gnomAD: MAF in the South Asian population 0.3867<br>https://gnomad.broadinstitute.org/variant/X-154133316-CA-C
c.4692delC
Case#: 19
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1% (Severe Phenotype), No 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: NM_000132.3:c.4692del (p.Leu1566Ter)
ClinVar: NA
CAID: CA1139532037
gnomAD: NA
020–2015
Case#: 020-2015
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.5612T>G
LegacyVariant:
ClinVar: No
CAID: CA414908197
gnomAD:
004–2025
Case#: 004-2025
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.328A>G
LegacyVariant:
ClinVar: No
CAID: CA255057
gnomAD:
001–2049
Case#: 001-2049
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:
004–2007
Case#: 004-2007
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.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
045–2002
Case#: 045-2002
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.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
003–2012
Case#: 003-2012
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.992T>C
LegacyVariant:
ClinVar: No
CAID: CA414917621
gnomAD:
003–2017
Case#: 003-2017
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: NM_000132.3:c.4379dupA
LegacyVariant:
ClinVar: No
CAID: CA645292749
gnomAD:
020–2052
Case#: 020-2052
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:
003–2007
Case#: 003-2007
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.1475A>G
LegacyVariant:
ClinVar: No
CAID: CA337334224
gnomAD:
087–2003
Case#: 087-2003
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.5122C>T
LegacyVariant:
ClinVar: No
CAID: CA120919
gnomAD:
038–2016
Case#: 038-2016
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:
020–2045
Case#: 020-2045
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.458A>T
LegacyVariant:
ClinVar: No
CAID: CA414919676
gnomAD:
084–2006
Case#: 084-2006
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.1910A>G
LegacyVariant:
ClinVar: No
CAID: CA414909849
gnomAD:
001–2045
Case#: 001-2045
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.1462G>A
LegacyVariant:
ClinVar: No
CAID: CA414912862
gnomAD:
071–2032
Case#: 071-2032
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.308_319delGTGGTCATTACA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
001–2028
Case#: 001-2028
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:
038–2020
Case#: 038-2020
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.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
035–2017
Case#: 035-2017
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:
S4
Case#: S4, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
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:
S11
Case#: S11, 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:
S14
Case#: S14, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
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: NM_000132.3:c.575T>C
LegacyVariant:
ClinVar: No
CAID: CA414919417
gnomAD:
Table 1
Case#: Cz8, 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: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/
CAID: NA
gnomAD: Not reported
Table 1
Case#: Cz17, 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.3224del (p.Ala1075ValfsTer4)
ClinVar: NA
CAID: NA
gnomAD: Not reported
Table 2
Case#: Cz4, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 2.4%
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 1
Case#: Cz38, 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: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/
CAID: NA
gnomAD: Not reported
Table 2
Case#: Cz10, 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 1
Case#: Cz16, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3(F8):c.5953C>T (p.Arg1985Ter)
ClinVar: 10300 https://www.ncbi.nlm.nih.gov/clinvar/variation/10300/
CAID: CA255191
gnomAD: Not reported
Table 2
Case#: Cz27, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 3.5%
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
B79 – B82
Case#: B79 - B82
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 7, FVIII:AG = 15, 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.6413C>A
LegacyVariant:
ClinVar: No
CAID: CA255204
gnomAD:
B28. B29
Case#: B28, B29
DiseaseAssertion: NA
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 78, FVIII:AG = 94, 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.2089G>C
LegacyVariant:
ClinVar: No
CAID: CA414909014
gnomAD:
A4
Case#: A4
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 6, FVIII:AG = 15, 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.896A>T
LegacyVariant:
ClinVar: No
CAID: CA255078
gnomAD:
Arg-4Leu (Arg43Leu)
Case#: HB-KHF-25 (Male, Korean)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: Among the 33 patients, 13 had a family history (39%), while the rest of the patients did not (sporadic, 61%). 27 patients (82%) had the severe form of the disease, while 6 patients (18%) had the moderate form
ParentalTesting: N/A
CasePresentingHPOs: HP:0003645, HP:0011858
CaseHPOsFreeText: Prolonged partial thromboplastin time, reduced factor IX activity
CaseNotHPOs: None
CasePreviousTesting: aPTT and one-stage clotting assay at labs where patients were ascertained: FIX-deficient plasma (STA®-Deficient IX; Diagnostica Stago, Asnieres-sur-Seine, France; reference range, 60–150%) at Samsung Medical Center or HemosIL™ (Instrumentation Laboratory, Milan, Italy; reference range, 50–145%) at the Korea Hemophilia Foundation.
Gene: F9
Variant: NM_000133.4:c.128G>T (p.Arg43Leu)
ClinVar: 993549
CAID: CA414435545
gnomAD: Absent/Not Reported
12
Case#: 12
DiseaseAssertion: NA
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Na
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.434G>A
LegacyVariant:
ClinVar: No
CAID: CA414438950
gnomAD:
22
Case#: 22
DiseaseAssertion: Hemophilia B, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 19.5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: All exons, UTRs, exon-intron junction regions, and the promotor of F9 were amplified by PCR and analyzed by direct DNA sequencing
Gene: F9
Variant: NM_000133.3:c.571C>T
LegacyVariant:
ClinVar: No
CAID: CA255340
gnomAD:
13
Case#: 13
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C = 3.7%
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.374G>A
LegacyVariant:
ClinVar: No
CAID: CA414437883
gnomAD:
UQU-HB3
Case#: UQU-HB3, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, PTT 50.9, Disabled left ankle
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A (p.Asp194Asn)
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
UQU-HB9
Case#: UQU-HB9, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Moderate, PTT 51.4, Unable to flex knees fully
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
UQU-HB11
Case#: UQU-HB11, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0001892 (Abnormal bleeding)
CaseHPOFreeText: Severe, Unable to flex elbows fully, PTT 148.3
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.4(F9):c.855G>C (p.Glu285Asp)
ClinVar: 828138 https://www.ncbi.nlm.nih.gov/clinvar/variation/828138/
CAID: CA414444506
gnomAD: Not reported
c.109G>A (p.Ala37Thr)
Case#: Odnoczko_Case (male, 74 y/o, in Poland)
DiseaseAssertion: Severe Hemophilia B (only in patients who receive vitamin K antagnoists (VKAs). The authors believe that during VKA therapy, the FIX activity is much lower than that of other vitamin K-dependent clotting factors for cases with this variant.
FamilyInfo: Family history of bleeding diathesis was negative
ParentalTesting:
CasePresentingHPOs: HP:0012233, HP:0031364, HP:0001892
CaseHPOsFreeText: left thigh & buttock hematoma, ecchymosis on extremeties with no mucosal bleeding, bleeding diathesis
CasePreviousTesting: local labaratory blood tests revealed anemia (hemoglobin concentration 8 g/dl; ref. range 14–18 g/dl), prolongation of prothrombin time (PT) with International Normalized Ratio (INR) within the therapeutic range (between 2.0 and 3.0). The proband's activated partial thromboplastin time (APTT) was significantly (>2-folds) prolonged and FIX activity markedly decreased
Gene: F9
Variant: NM_000133.4:c.109G>A (p.Ala37Thr)
ClinVar: 804089
CAID: CA10529736
gnomAD: Allele Frequency in population where variant was found in the highest (South Asian population): 0.0001128
mutation
Case#: Mutation found in 4 patients, and in 4 families
DiseaseAssertion: Severe in 2 cases, moderate in the other 2 cases
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858, HP:0003645, HP:0001892
CaseHPOsFreeText: reduced factor IX activity, activated partial thromboplastin time (APTT), normal FVIII clotting activity and bleeding tendency
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
Case#: Patient HB401 (Hispanic; Male)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: None
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: FIX Coagulant Activity: 1%
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.50T>A (p.Ile17Asn)
LegacyVariant: c.79T>A (p.Ile-30Asn)
ClinVar: Absent
CAID: CA414434315
gnomAD: Absent/Not Reported
identify the causative mutation
Case#: Belvini_Proband_14 (male, Italian)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
LegacyVariant:
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
Case#: Patient 63 (Spanish origin; assumed male)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: Not available
ParentalTesting: Not available
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: FIX:C = 3 (reduced factor IX activity)
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
Case#: Patient 66 (Spanish origin; assumed male)
DiseaseAssertion: Mild Hemophilia B
FamilyInfo: Not available
ParentalTesting: Not available
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: Factor IX: C = 30% (reduced factor IX activity)
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4(F9):c.19A>T (p.Ile7Phe)
LegacyVariant: c.48A>T (p.Ile-40Phe)
ClinVar: 367997
CAID: CA10529708
gnomAD: Filtering AF: 0.0007752 (no homozygotes)
Case#: Patient 72 (Spanish origin; assumed male)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: Not available
ParentalTesting: Not available
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: FIX:C = <1 (reduced factor IX activity)
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
For p.Ser577Tyr mutation (patient P4)
Case#: P4 (female)
DiseaseAssertion: Carrier
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0003125, HP:0001928
CaseHPOFreeText: Low FVIII levels (FVIII:Ag showed a moderate reduction (29.8% ± 1.7, p < 0.01) compared to the WT; FVIII:C undetectable), abnormal blood coagulation
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.
Gene: F8
Variant: NM_000132.4:c.1730C>A
CAID: CA414911649
gnomAD: Absent/Not Reported
C.6427A>G
Case#: 28
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
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.6427A>G (p.Met2124Val)
ClinVar: NA
CAID: CA414899297
gnomAD: Not reported
c.1910A>T
Case#: 23
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Moderate
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.1910A>T (p.Asn618Ile)
ClinVar: NA
CAID: CA414909847
gnomAD: Not reported
c.1180G>T
Case#: 18, Spanish
DiseaseAssertion: Hemophilia A
FamilyInfo: Positive
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.1180G>T (p.Ala375Ser)
ClinVar: NA
CAID: CA414916327
gnomAD: Not reported
c.5805T>A
Case#: 8
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe
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.5805T>A (p.Tyr1935Ter)
ClinVar: NA
CAID: CA414906924
gnomAD: Not Reported
c.1251insC
Case#: 1
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe
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.1251_1252insC (p.Val418ArgfsTer6)
ClinVar: NA
CAID: CA1139532040
gnomAD: Not reported
Arg-4Leu
Case#: 37HBT150 (Turkish; assumed male)
DiseaseAssertion: Moderate Hemophilia B
FamilyInfo: N/A
ParentalTesting: Not provided
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: Reduced factor IX activity (FIX:C: 1.3)
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>T (p.Arg43Leu)
LegacyVariant: c.6365 G>T (p.Arg-4Leu)
ClinVar: 993549
CAID: CA414435545
gnomAD: Absent/Not Reported
mutation
Case#: HB-125 (assumed male, India)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C <1%)
CaseNotHPOs: None
CasePreviousTesting: None
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
mutation
Case#: Heit_Proband_HB535 (assumed male, AmerIndian from Peru)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (FIX:C: <1%)
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
LegacyVariant: c.6364C>T (Arg-4Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Absent/Not Reported
c.110C > T p (Ala37Val).
Case#: Mülling_Proband_1 (55 y/o, male)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858, HP:0100584, HP:0002094
CaseHPOsFreeText: Reduced factor IX activity (FIX activity: 3%), infective endocarditis, dyspnea
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.110C>T (p.Ala37Val)
ClinVar: Absent
CAID: CA414435437
gnomAD: 0.00002186 in European (non-Finnish) population (highest frequency of variant found in this population)
AdditionalCaseInfo: Patient developed severe bleeding under therapy with phenprocoumon, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors
mutations
Case#: Ghanem_Paris 2 (assumed male, from Paris) & Ghanem_ Caen 2 (assumed male, from Caen)
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: N/A
ParentalTesting: None
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (Paris 2: FIX:C: <1, FIX:Ag: 28, Caen 2: FIX:C: <1
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.127C>T (p.Arg43Trp)
ClinVar: 811505
CAID: CA414435537
gnomAD: Highest AF (South Asian population): 0.0004904
Variant
Case#: Calgary 15
DiseaseAssertion: Hemophilia B (severity not provided)
FamilyInfo: None
ParentalTesting: N/A
CasePresentingHPOs: HP:0011858
CaseHPOsFreeText: reduced factor IX activity (does not specify severity for probands) "patients from these kindreds have various disease severity, with plasma factor IX activity from < 0.01 U/mL to 0.30 U/mL." "FIX antigen was not available from patients from 6 kindreds, reduced in seven, normal in six, and not available from six."
CaseNotHPOs: None
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.128G>A (p.Arg43Gln)
LegacyVariant: c.6365 G>A (p.Arg-4Gln)
ClinVar: 810864
CAID: CA414435539
gnomAD: Absent/Not Reported
I17N
Case#: N/A
DiseaseAssertion: Severe Hemophilia B
FamilyInfo: None
ParentalTesting: None
CasePresentingHPOs: HP:0001929
CaseHPOsFreeText: reduced factor IX activity
CaseNotHPOs: N/A
CasePreviousTesting: N/A
Gene: F9
Variant: NM_000133.4:c.50T>A (p.Ile17Asn)
ClinVar: Absent
CAID: CA414434315
gnomAD: Absent/Not Reported