Case: Patient 6 (Family C), male, 53yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group O, Platelet count x103/μl = 193, PFA 100 sec = 199, SPA % = 5.2, MADR mg/mL = 0.75, VWF:Ag U/dL = 47.1, VWF:CB U/dL = 44.6, VWF:CB ratio = 0.94, VWF:RCo U/dL = 38.0, VWF:RCo ratio = 0.80, Platelet VWF U/dL = 47.4, FVIII U/dL = 43.8, BAT F/M = 0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Case: Patient 10 (Family D), female, 24yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group AB, Platelet count x103/μl = 231, PFA 100 sec = 223, SPA % = 6, MADR mg/mL = 0.75, VWF:Ag U/dL = 46.0, VWF:CB U/dL = 49.1, VWF:CB ratio = 1.07, VWF:RCo U/dL = 40.5, VWF:RCo ratio = 0.83, Platelet VWF U/dL = 55.6, FVIII U/dL = 64.8, BAT F/M = NA

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Case: Patient 11 (Family E), male, 11yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group O, Platelet count x103/μl = 220, PFA 100 sec = >300, SPA % = 11.3, MADR mg/mL = 0.3, VWF:Ag U/dL = 28.8, VWF:CB U/dL = 28.4, VWF:CB ratio = 0.98, VWF:RCo U/dL = 23.0, VWF:RCo ratio = 0.80, Platelet VWF U/dL = 54.1, FVIII U/dL = 51.5, BAT F/M = 5

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4021C>T (p.Arg1341Trp)

HGVS: NM_000552.4(VWF):c.4021C>T (p.Arg1341Trp)

ClinVarID: 100316; https://www.ncbi.nlm.nih.gov/clinvar/variation/100316/

CAID: NA

gnomAD: MAF = 0.00008674 (3/34586 alleles) in the Latino/Admixed American population; https://gnomad.broadinstitute.org/variant/12-6128563-G-A?dataset=gnomad_r2_1

Case: Patient 8 (Family D), male, 49yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group A, Platelet count x103/μl = 252, PFA 100 sec = 175, SPA % = 0, MADR mg/mL = 0.6, VWF:Ag U/dL = 54.3, VWF:CB U/dL = 55.1, VWF:CB ratio = 1.01, VWF:RCo U/dL = 51.6, VWF:RCo ratio = 0.94, Platelet VWF U/dL = 60.3, FVIII U/dL = 62.2, BAT F/M = NA

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Variant 2: c.3797C>A (p.Pro1266Gln)

HGVS: NM_000552.4(VWF):c.3797C>A (p.Pro1266Gln)

ClinVarID: 100279; https://www.ncbi.nlm.nih.gov/clinvar/variation/100279/

CAID: NA

gnomAD: MAF = 0.001346 (41/30468 alleles; 2 homozygotes) in the South Asian population; https://gnomad.broadinstitute.org/variant/12-6128787-G-T?dataset=gnomad_r2_1

Case: Patient 12 (Family F), female, 50yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group A, Platelet count x103/μl = 204, PFA 100 sec = 91, SPA % = 10, MADR mg/mL = 0.45, VWF:Ag U/dL = 108, VWF:CB U/dL = 101.9, VWF:CB ratio = 0.94, VWF:RCo U/dL = 97.7, VWF:RCo ratio = 0.91, Platelet VWF U/dL = 136.4, FVIII U/dL = 107.5, BAT F/M = 16

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.3797C>A (p.Pro1266Gln)

HGVS: NM_000552.4(VWF):c.3797C>A (p.Pro1266Gln)

ClinVarID: 100279; https://www.ncbi.nlm.nih.gov/clinvar/variation/100279/

CAID: NA

gnomAD: MAF = 0.001346 (41/30468 alleles; 2 homozygotes) in the South Asian population; https://gnomad.broadinstitute.org/variant/12-6128787-G-T?dataset=gnomad_r2_1

Case: Patient 5 (Family C), female, 50yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group O, Platelet count x103/μl = 211, PFA 100 sec = 210, SPA % = 10, MADR mg/mL = 0.6, VWF:Ag U/dL = 40.6, VWF:CB U/dL = 42.8, VWF:CB ratio = 1.1, VWF:RCo U/dL = NA, VWF:RCo ratio = NA, Platelet VWF U/dL = 41.2, FVIII U/dL = 62.8, BAT F/M = 8

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Case: Patient 7 (Family C), female, 21yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group O, Platelet count x103/μl = 293, PFA 100 sec = >300, SPA % = 6, MADR mg/mL = 0.6, VWF:Ag U/dL = 26.7, VWF:CB U/dL = 27.2, VWF:CB ratio = 1.01, VWF:RCo U/dL = 25.8, VWF:RCo ratio = 0.92, Platelet VWF U/dL = 59.1, FVIII U/dL = 40.9, BAT F/M = 6

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Case: Patient 9 (Family D), male, 18yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group A, Platelet count x103/μl = 231, PFA 100 sec = 95, SPA % = 0, MADR mg/mL = 0.75, VWF:Ag U/dL = 151.1, VWF:CB U/dL = 175.5, VWF:CB ratio = 1.16, VWF:RCo U/dL = 153.5, VWF:RCo ratio = 0.87, Platelet VWF U/dL = 95.2, FVIII U/dL = 148.2, BAT F/M = NA

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.3797C>A (p.Pro1266Gln)

HGVS: NM_000552.4(VWF):c.3797C>A (p.Pro1266Gln)

ClinVarID: 100279; https://www.ncbi.nlm.nih.gov/clinvar/variation/100279/

CAID: NA

gnomAD: MAF = 0.001346 (41/30468 alleles; 2 homozygotes) in the South Asian population; https://gnomad.broadinstitute.org/variant/12-6128787-G-T?dataset=gnomad_r2_1

Case: Patient 4 (Family C), female, 76yo

DiseaseAssertion: VWD2B

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0030129, HP:0030130, HP:0011871, HP:0012147

(impaired ristocetin cofactor assay activity, Impaired von Willebrand factor collagen binding activity, Impaired RIPA, Reduced quantity of VWF)

CaseHPOFreeText: blood group O, Platelet count x103/μl = 236, PFA 100 sec = >300, SPA % = 8.4, MADR mg/mL = 0.75, VWF:Ag U/dL = 35.4, VWF:CB U/dL = 37.3, VWF:CB ratio = 1.05, VWF:RCo U/dL = 25.4, VWF:RCo ratio = 0.72, Platelet VWF U/dL = 66.8, FVIII U/dL = 32.0, BAT F/M = 16

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 28 of VWF

PreviouslyPublished: NA

Gene: VWF

Variant: c.4135C>T (p.Arg1379Cys)

HGVS: NM_000552.4(VWF):c.4135C>T (p.Arg1379Cys)

ClinVarID: 100333; https://www.ncbi.nlm.nih.gov/clinvar/variation/100333/

CAID: NA

gnomAD: MAF = 0.00003891 (5/128500 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128449-G-A?dataset=gnomad_r2_1

Case: P53, Chinese, female, 70yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeText: HP:0012147

(Reduced quantity of VWF)

CaseNOTHPOs: type O blood, bleeding score = 9; VWF:Ag (%) = 32.1, VWF:RCo (%) = 6.0, FVIII:C (%) = 50.8, VWF:CB (%) = 14.7, VWFpp (%) = 56.9, VWF:RCo/VWF:Ag = 0.2, VWF:CB/VWF:Ag = 0.5, VWFpp/VWF:Ag = 1.8, FVIII:C/VWF:Ag = 1.6

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4790G>T (p.Arg1597Leu)

HGVS: NM_000552.4(VWF):c.4790G>T (p.Arg1597Leu)

ClinVarID: 100392; https://www.ncbi.nlm.nih.gov/clinvar/variation/100392/

CAID: NA

gnomAD: absent

Case: P44, Chinese, male, 6yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 6; VWF:Ag (%) = 43.6, VWF:RCo (%) = 18.3, FVIII:C (%) = 38.7, VWF:CB (%) = 16.7, VWFpp (%) = 64.8, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.4, VWFpp/VWF:Ag = 1.5, FVIII:C/VWF:Ag = 0.9

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.1870G>A (p.Gly624Ser)

HGVS: NM_000552.4(VWF):c.1870G>A (p.Gly624Ser)

ClinVarID: 619737; https://www.ncbi.nlm.nih.gov/clinvar/variation/619737/

CAID: NA

gnomAD: MAF = 0.004886 (59/12076 alleles; 1 homozygote) in the East Asian population; https://gnomad.broadinstitute.org/variant/12-6166098-C-T?dataset=gnomad_r2_1

Variant 2: c.4883T>C (p.Ile1628Thr)

HGVS: NM_000552.4(VWF):c.4883T>C (p.Ile1628Thr)

ClinVarID: 284; https://www.ncbi.nlm.nih.gov/clinvar/variation/284/

CAID: NA

gnomAD: absent

Case: P19, Chinese, male, 35yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 4; VWF:Ag (%) = 17.5, VWF:RCo (%) = 5.1, FVIII:C (%) = 35.9, VWF:CB (%) = 16.9, VWFpp (%) = 45.3, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 2.6, FVIII:C/VWF:Ag = 2.1

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4120C>T (p.Arg1374Cys)

HGVS: NM_000552.4(VWF):c.4120C>T (p.Arg1374Cys)

ClinVarID: 100329; https://www.ncbi.nlm.nih.gov/clinvar/variation/100329/

CAID: NA

gnomAD: MAF = 0.000008824 (1/113322 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6128464-G-A?dataset=gnomad_r2_1

Case: P63, Chinese, female, 23yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 15; VWF:Ag (%) = 1.2, VWF:RCo (%) = 0.5, FVIII:C (%) = 5.9, VWF:CB (%) = 0.6, VWFpp (%) = 0.5, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.5, VWFpp/VWF:Ag = 0.4, FVIII:C/VWF:Ag = 4.9

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.817C>T (p.Arg273Trp)

HGVS: NM_000552.4(VWF):c.817C>T (p.Arg273Trp)

ClinVarID: 100493; https://www.ncbi.nlm.nih.gov/clinvar/variation/100493/

CAID: NA

gnomAD: MAF = 0.00005288 (6/113462 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6184558-G-A?dataset=gnomad_r2_1

Variant 2: c.5335C>T (p.Arg1779Ter)

HGVS: NM_000552.4(VWF):c.5335C>T (p.Arg1779Ter)

ClinVarID: 100425; https://www.ncbi.nlm.nih.gov/clinvar/variation/100425/

CAID: NA

gnomAD: absent

Case: P76, Chinese, male, 21yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 3; VWF:Ag (%) = 4.7, VWF:RCo (%) = 5.4, FVIII:C (%) = 27.2, VWF:CB (%) = 5.5, VWFpp (%) = 4.3, VWF:RCo/VWF:Ag = 1.1, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 0.9, FVIII:C/VWF:Ag = 5.8, RIPA (1.2 mg/ml, %) = 73.4

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: Exon1-exon5 del - Unregistered Variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Variant 2: c.7464C>T (p.Gly2488=) - reported to be a splice site variant

HGVS: NM_000552.4(VWF):c.7464C>T (p.Gly2488=)

ClinVarID: 619755; https://www.ncbi.nlm.nih.gov/clinvar/variation/619755/

CAID: NA

gnomAD: MAF = 0.000008799 (1/113644 alleles) in the European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6080849-G-A?dataset=gnomad_r2_1

Case: P46, Chinese, female, 55yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 14; VWF:Ag (%) = 45.4, VWF:RCo (%) = 44.5, FVIII:C (%) = 76.9, VWF:CB (%) = 54.9, VWFpp (%) = 43.2, VWF:RCo/VWF:Ag = 1.0, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 1.0, FVIII:C/VWF:Ag = 1.7

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4414G>C (p.Asp1472His)

HGVS: NM_000552.4(VWF):c.4414G>C (p.Asp1472His)

ClinVarID: 256679; https://www.ncbi.nlm.nih.gov/clinvar/variation/256679/

CAID: NA

gnomAD: MAF = 0.5077 (12039/23712 alleles; 3078 homozygotes) in African/African-American population; https://gnomad.broadinstitute.org/variant/12-6128170-C-G?dataset=gnomad_r2_1

Case: P12, Chinese, Male, 11yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 6; VWF:Ag (%) = 15.8, VWF:RCo (%) = 7.3, FVIII:C (%) = 45.5, VWF:CB (%) = 4.1, VWFpp (%) = 50.3, VWF:RCo/VWF:Ag = 0.5, VWF:CB/VWF:Ag = 0.3, VWFpp/VWF:Ag = 3.2, FVIII:C/VWF:Ag = 2.9

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4517C>T (p.Ser1506Leu)

HGVS: NM_000552.4(VWF):c.4517C>T (p.Ser1506Leu)

ClinVarID: 100369; https://www.ncbi.nlm.nih.gov/clinvar/variation/100369/

CAID: NA

gnomAD: absent

Case: P16, Chinese, female, 25yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 15; VWF:Ag (%) = 2.1, VWF:RCo (%) = 1.9, FVIII:C (%) = 4.3, VWF:CB (%) = 1.7, VWFpp (%) = 1.5, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 0.8, VWFpp/VWF:Ag = 0.7, FVIII:C/VWF:Ag = 2.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.1093C>T (p.Arg365Ter)

HGVS: NM_000552.4(VWF):c.1093C>T (p.Arg365Ter)

ClinVarID: 100172; https://www.ncbi.nlm.nih.gov/clinvar/variation/100172/

CAID: NA

gnomAD: absent

Variant 2: c.8116–2delA - Unregistered variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Case: P70, Chinese, female, 51yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 2; VWF:Ag (%) = 28.3, VWF:RCo (%) = 36.6, FVIII:C (%) = 61.3, VWF:CB (%) = 34.6, VWFpp (%) = 64.5, VWF:RCo/VWF:Ag = 1.3, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 2.3, FVIII:C/VWF:Ag = 2.2

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.6554G>A (p.Arg2185Gln)

HGVS: NM_000552.4(VWF):c.6554G>A (p.Arg2185Gln)

ClinVarID: 100443; https://www.ncbi.nlm.nih.gov/clinvar/variation/100443/

CAID: NA

gnomAD: MAF = 0.1899 (4712/24810 alleles; 465 homozygotes) in the African/African-American population; https://gnomad.broadinstitute.org/variant/12-6103072-C-T?dataset=gnomad_r2_1

Case: P56, Chinese, male, 6yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 13; VWF:Ag (%) = 15.4, VWF:RCo (%) = 7.1, FVIII:C (%) = 43.3, VWF:CB (%) = 2.4, VWFpp (%) = 43.8, VWF:RCo/VWF:Ag = 0.5, VWF:CB/VWF:Ag = 0.2, VWFpp/VWF:Ag = 2.8, FVIII:C/VWF:Ag = 2.8

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4517C>T (p.Ser1506Leu)

HGVS: NM_000552.4(VWF):c.4517C>T (p.Ser1506Leu)

ClinVarID: 100369; https://www.ncbi.nlm.nih.gov/clinvar/variation/100369/

CAID: NA

gnomAD: absent

Case: P25, Chinese, female, 23yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 5; VWF:Ag (%) = 15.6, VWF:RCo (%) = 4.4, FVIII:C (%) = 31.0, VWF:CB (%) = 14.2, VWFpp (%) = 47.7, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 3.1, FVIII:C/VWF:Ag = 2.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4121G>A (p.Arg1374His)

HGVS: NM_000552.4(VWF):c.4121G>A (p.Arg1374His)

ClinVarID: 100330; https://www.ncbi.nlm.nih.gov/clinvar/variation/100330/

CAID: NA

gnomAD: absent

Case: P14, Chinese, female, 3yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 5; VWF:Ag (%) = 18.2, VWF:RCo (%) = 7.6, FVIII:C (%) = 29.1, VWF:CB (%) = 17.5, VWFpp (%) = 45.6, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 2.5, FVIII:C/VWF:Ag = 1.6

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4121G>A (p.Arg1374His)

HGVS: NM_000552.4(VWF):c.4121G>A (p.Arg1374His)

ClinVarID: 100330; https://www.ncbi.nlm.nih.gov/clinvar/variation/100330/

CAID: NA

gnomAD: absent

Case: P84, Chinese, female, 36yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 5; VWF:Ag (%) = 26.6, VWF:RCo (%) = 3.3, FVIII:C (%) = 41.7, VWF:CB (%) = 25.2, VWFpp (%) = 41.1, VWF:RCo/VWF:Ag = 0.1, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 1.6, FVIII:C/VWF:Ag = 1.6

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4121G>A (p.Arg1374His)

HGVS: NM_000552.4(VWF):c.4121G>A (p.Arg1374His)

ClinVarID: 100330; https://www.ncbi.nlm.nih.gov/clinvar/variation/100330/

CAID: NA

gnomAD: absent

Case: P13, Chinese, male, 8yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 5; VWF:Ag (%) = 21.6, VWF:RCo (%) = 9.4, FVIII:C (%) = 53.2, VWF:CB (%) = 5.7, VWFpp (%) = 56.1, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.3, VWFpp/VWF:Ag = 2.6, FVIII:C/VWF:Ag = 2.5

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4517C>T (p.Ser1506Leu)

HGVS: NM_000552.4(VWF):c.4517C>T (p.Ser1506Leu)

ClinVarID: 100369; https://www.ncbi.nlm.nih.gov/clinvar/variation/100369/

CAID: NA

gnomAD: absent

Case: P65, Chinese, female, 24yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 3; VWF:Ag (%) = 55.7, VWF:RCo (%) = 51.2, FVIII:C (%) = 72.7, VWF:CB (%) = 57.1, VWFpp (%) = 61.7, VWF:RCo/VWF:Ag = 0.9, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 1.1, FVIII:C/VWF:Ag = 1.3

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4499C>T (p.Ala1500Val)

HGVS: NM_000552.4(VWF):c.4499C>T (p.Ala1500Val)

ClinVarID: 439339; https://www.ncbi.nlm.nih.gov/clinvar/variation/439339/

CAID: NA

gnomAD: MAF = 0.003511 (70/19938 alleles) in the East Asain population; https://gnomad.broadinstitute.org/variant/12-6128085-G-A?dataset=gnomad_r2_1

Case: P4, Chinese, male, 35yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 6; VWF:Ag (%) = 22.6, VWF:RCo (%) = 5.0, FVIII:C (%) = 36.6, VWF:CB (%) = 25.4, VWFpp (%) = 43.0, VWF:RCo/VWF:Ag = 0.2, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 1.9, FVIII:C/VWF:Ag = 1.6

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4121G>A (p.Arg1374His)

HGVS: NM_000552.4(VWF):c.4121G>A (p.Arg1374His)

ClinVarID: 100330; https://www.ncbi.nlm.nih.gov/clinvar/variation/100330/

CAID: NA

gnomAD: absent

Case: P79, Chinese, female, 24yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 9; VWF:Ag (%) = 0.5, VWF:RCo (%) = <0.5, FVIII:C (%) = 5.7, VWF:CB (%) = <0.5, VWFpp (%) = <0.5, VWF:RCo/VWF:Ag = NA, VWF:CB/VWF:Ag = NA, VWFpp/VWF:Ag = NA, FVIII:C/VWF:Ag = 11.4

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.1093C>T (p.Arg365Ter)

HGVS: NM_000552.4(VWF):c.1093C>T (p.Arg365Ter)

ClinVarID: 100172; https://www.ncbi.nlm.nih.gov/clinvar/variation/100172/

CAID: NA

gnomAD: absent

Variant 2: c.4975C>T (p.Arg1659Ter)

HGVS: NM_000552.4(VWF):c.4975C>T (p.Arg1659Ter)

ClinVarID: 297; https://www.ncbi.nlm.nih.gov/clinvar/variation/297/

CAID: NA

gnomAD: MAF = 0.0004007 (10/24958 alleles) in the European (Finnish) population; https://gnomad.broadinstitute.org/variant/12-6127609-G-A?dataset=gnomad_r2_1

Case: P45, Chinese, female, 8yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type A blood, bleeding score = 4; VWF:Ag (%) = 23.5, VWF:RCo (%) = 6.5, FVIII:C (%) = 40.0, VWF:CB (%) = 15.2, VWFpp (%) = 44.5, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.6, VWFpp/VWF:Ag = 1.9, FVIII:C/VWF:Ag = 1.7

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4628C>T (p.Ser1543Phe)

HGVS: NM_000552.4(VWF):c.4628C>T (p.Ser1543Phe)

ClinVarID: 100376; https://www.ncbi.nlm.nih.gov/clinvar/variation/100376/

CAID: NA

gnomAD: absent

Case: P52, Chinese, female, 55yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 9; VWF:Ag (%) = 19.1, VWF:RCo (%) = 3.1, FVIII:C (%) = 35.8, VWF:CB (%) = 22.7, VWFpp (%) = 50.3, VWF:RCo/VWF:Ag = 0.2, VWF:CB/VWF:Ag = 1.2, VWFpp/VWF:Ag = 2.6, FVIII:C/VWF:Ag = 1.9

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4120C>A (p.Arg1374Ser)

HGVS: NM_000552.4(VWF):c.4120C>A (p.Arg1374Ser)

ClinVarID: 100328; https://www.ncbi.nlm.nih.gov/clinvar/variation/100328/

CAID: NA

gnomAD: absent

Case: P26, Chinese, female, 30yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type AB blood, bleeding score = 14; VWF:Ag (%) = 11.3, VWF:RCo (%) = 3.7, FVIII:C (%) = 45.0, VWF:CB (%) = 4.0, VWFpp (%) = 41.7, VWF:RCo/VWF:Ag = 0.3, VWF:CB/VWF:Ag = 0.4, VWFpp/VWF:Ag = 3.7, FVIII:C/VWF:Ag = 4.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4517C>T (p.Ser1506Leu)

HGVS: NM_000552.4(VWF):c.4517C>T (p.Ser1506Leu)

ClinVarID: 100369; https://www.ncbi.nlm.nih.gov/clinvar/variation/100369/

CAID: NA

gnomAD: absent

Case: P3, Chinese, male, 7yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 5; VWF:Ag (%) = 13.0, VWF:RCo (%) = 5.0, FVIII:C (%) = 39.1, VWF:CB (%) = 3.5, VWFpp (%) = 46.8, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.3, VWFpp/VWF:Ag = 3.6, FVIII:C/VWF:Ag = 3.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4517C>T (p.Ser1506Leu)

HGVS: NM_000552.4(VWF):c.4517C>T (p.Ser1506Leu)

ClinVarID: 100369; https://www.ncbi.nlm.nih.gov/clinvar/variation/100369/

CAID: NA

gnomAD: absent

Case: P58, Chinese, female, 27yo

DiseaseAssertion: VWD2A

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs:

CaseHPOFreeText: HP:0012147

(Reduced quantity of VWF)

CaseNOTHPOs: type O blood, bleeding score = 8; VWF:Ag (%) = 17.1, VWF:RCo (%) = 2.3, FVIII:C (%) = 44.3, VWF:CB (%) = 3.7, VWFpp (%) = 41.1, VWF:RCo/VWF:Ag = 0.1, VWF:CB/VWF:Ag = 0.2, VWFpp/VWF:Ag = 2.4, FVIII:C/VWF:Ag = 2.6

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4790G>T (p.Arg1597Leu)

HGVS: NM_000552.4(VWF):c.4790G>T (p.Arg1597Leu)

ClinVarID: 100392; https://www.ncbi.nlm.nih.gov/clinvar/variation/100392/

CAID: NA

gnomAD: absent

Case: P17, Chinese, female, 20yo

DiseaseAssertion: VWD2M

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type B blood, bleeding score = 10; VWF:Ag (%) = 17.6, VWF:RCo (%) = 7.3, FVIII:C (%) = 35.8, VWF:CB (%) = 15.8, VWFpp (%) = 51.9, VWF:RCo/VWF:Ag = 0.4, VWF:CB/VWF:Ag = 0.9, VWFpp/VWF:Ag = 2.9, FVIII:C/VWF:Ag = 2.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.3389G>T (p.Cys1130Phe)

HGVS: NM_000552.4(VWF):c.3389G>T (p.Cys1130Phe)

ClinVarID: 100261; https://www.ncbi.nlm.nih.gov/clinvar/variation/100261/

CAID: NA

gnomAD: absent

Case: P31, Chinese, female, 21yo

DiseaseAssertion: VWD3

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 15; VWF:Ag (%) = 1.0, VWF:RCo (%) = 0.7, FVIII:C (%) = 4.1, VWF:CB (%) = 0.8, VWFpp (%) = 0.8, VWF:RCo/VWF:Ag = 0.7, VWF:CB/VWF:Ag = 0.8, VWFpp/VWF:Ag = 0.8, FVIII:C/VWF:Ag = 4.1

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.953_954insG - Unregistered Variant

HGVS: NA

ClinVarID: NA

CAID: NA

gnomAD: NA

Variant 2: c.4368C>G (p.Tyr1456Ter)

HGVS: NM_000552.4(VWF):c.4368C>G (p.Tyr1456Ter)

ClinVarID: 100350; https://www.ncbi.nlm.nih.gov/clinvar/variation/100350/

CAID: NA

gnomAD: absent

Case: P66, Chinese, male, 27yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: type O blood, bleeding score = 1; VWF:Ag (%) = 56.0, VWF:RCo (%) = 43.4, FVIII:C (%) = 70.0, VWF:CB (%) = 58.9, VWFpp (%) = 53.6, VWF:RCo/VWF:Ag = 0.8, VWF:CB/VWF:Ag = 1.1, VWFpp/VWF:Ag = 1.0, FVIII:C/VWF:Ag = 1.3

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.4414G>C (p.Asp1472His)

HGVS: NM_000552.4(VWF):c.4414G>C (p.Asp1472His)

ClinVarID: 256679; https://www.ncbi.nlm.nih.gov/clinvar/variation/256679/

CAID: NA

gnomAD: MAF = 0.5077 (12039/23712 alleles; 3078 homozygotes) in African/African-American population; https://gnomad.broadinstitute.org/variant/12-6128170-C-G?dataset=gnomad_r2_1

Case: P32, Chinese, male, 3yo

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147

(Reduced quantity of VWF)

CaseHPOFreeText: patient coexisting with severe haemophilia A; type O blood, bleeding score = 3; VWF:Ag (%) = 51.3, VWF:RCo (%) = 50.7, FVIII:C (%) = 1.0, VWF:CB (%) = 50.3, VWFpp (%) = 49.2, VWF:RCo/VWF:Ag = 1.0, VWF:CB/VWF:Ag = 1.0, VWFpp/VWF:Ag = 1.0, FVIII:C/VWF:Ag = 0.0

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NGS

PreviouslyPublished: NA

Gene: VWF

Variant: c.646G>A (p.Glu216Lys)

HGVS: NM_000552.5(VWF):c.646G>A (p.Glu216Lys)

ClinVarID: 870925; https://www.ncbi.nlm.nih.gov/clinvar/variation/870925/

CAID: NA

gnomAD: 0.001353 (27/19952 alleles) in East Asian population; https://gnomad.broadinstitute.org/variant/12-6204637-C-T?dataset=gnomad_r2_1

MultipleGeneVariants

Gene: F8

Variant: p.Arg446Ter - Unregistered Variant

Case UZ053: 28 year old female (row 54 in supplemental table)

DiseaseAssertion: type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext:vWF:Ag (%) = 20.4; vWF:GPIbR (%) = 22.1; Act/Ag ratio = 1.08; FVIII:C (%) = 58.9; Platelets (x10^9/L) = 261

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.449T>C p.Leu150Pro

HGVS:

ClinVarID: 100363

CAID:

gnomAD: 0.000001239 (2 in 1614236) no homozygotes https://gnomad.broadinstitute.org/variant/12-6110457-A-G?dataset=gnomad_r4

Case 14: 43 year old female, study ID UZ101 in supplemental table

DiseaseAssertion: type 2 NOS VWD presequencing, type 2A/M VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: vWF:Ag (%) = 23.6; vWF:GPIbR (%) = 9; Act/Ag ratio = 0.38; FVIII:C (%) = 35.3; Platelets (x10^9/L) = 244

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: 0.000003098 (5 in 1613796) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019298-G-A?dataset=gnomad_r4

Case UZ090: 4 year old female (row 91 in supplemental table)

DiseaseAssertion: type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370

CaseHPOFreeRext: vWF:Ag (%) = 15; vWF:GPIbR (%) = 14.1; Act/Ag ratio = 0.94; FVIII:C (%) = 9.1; Platelets (x10^9/L) = 395

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.2573G>T p.Cys858Phe

HGVS:

ClinVarID: 100229

CAID:

gnomAD: absent

MultipleGeneVariants:

Gene: VWF

Variant: c.7437+5G>A

ClinVarID: not found

gnomAD: 0.000001859 (3 in 1613728) no homozygotes https://gnomad.broadinstitute.org/variant/12-5976106-C-T?dataset=gnomad_r4

Case 8: 6 y.o. female, study ID UZ026 in supplemental table

DiseaseAssertion: type 2 NOS VWD presequencing, type 2M VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 30.2; vWF:GPIbR (%) = 8.5; Act/Ag ratio = 0.28; FVIII:C (%) = 32.4; Platelets (x10^9/L) = 503

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod:WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4195C>T p.Arg1399Cys

HGVS:

ClinVarID: 100337

CAID:

gnomAD: 0.00005143 (83/1613776) 0 homozygotes https://gnomad.broadinstitute.org/variant/12-6019223-G-A?dataset=gnomad_r4

Case 11: 37 year old female, study ID UZ022 in supplemental table

DiseaseAssertion: type 2 NOS VWD presequencing, type 2A VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: vWF:Ag (%) = 54.1; vWF:GPIbR (%) = 10.5; Act/Ag ratio = 0.19; FVIII:C (%) = 56.6; Platelets (x10^9/L) = 291

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.3569G>A p.Cys1190Tyr

HGVS:

ClinVarID: 626960

CAID:

gnomAD: 6.195e-7 (1 in 1614212) no homozygotes https://gnomad.broadinstitute.org/variant/12-6022005-C-T?dataset=gnomad_r4

MultipleGeneVariants: F7:c.977G>A p.Arg326Gln (VUS)

Case 15: 48 year old female, study ID UZ097 in supplemental table

DiseaseAssertion: type 2 NOS VWD presequencing, type 2B VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: vWF:Ag (%) = 34.3; vWF:GPIbR (%) = 17.2; Act/Ag ratio = 0.50; FVIII:C (%) = 44.5; Platelets (x10^9/L) = 344

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.3842T>C p.Leu1281Pro

HGVS:

ClinVarID: 627206

CAID:

gnomAD: absent

Case 12: 39 year old female, study ID UZ108

DiseaseAssertion: type 2 NOS VWD presequencing, type 2A VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: vWF:Ag (%) = 74.6; vWF:GPIbR (%) = 22.3; Act/Ag ratio = 0.30; FVIII:C (%) = 64; Platelets (x10^9/L) = 325

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod:WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.3569G>A p.Cys1190Tyr

HGVS:

ClinVarID: 626960

CAID:

gnomAD: 6.195e-7 (1 in 1614212) no homozygotes https://gnomad.broadinstitute.org/variant/12-6022005-C-T?dataset=gnomad_r4

Case UZ080: 0 year old female (row 81 in supplementary table)

DiseaseAssertion: type 2A/M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 17.9; vWF:GPIbR (%) = 5.5; Act/Ag ratio = 0.31; FVIII:C (%) = 19.7; Platelets (x10^9/L) = 324

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4121G>A p.Arg1374His

HGVS:

ClinVarID: 100330

CAID:

gnomAD: 0.000001239 (2 in 1613878) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019297-C-T?dataset=gnomad_r4

Case 16: 1 year old female, study ID UZ052 in supplemental table

DiseaseAssertion: type 3 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 1.5; vWF:GPIbR (%) = 0.6; Act/Ag ratio = 0.40; FVIII:C (%) = 12.2; Platelets (x10^9/L) = 369

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.421G>A p.Asp141Asn

HGVS:

ClinVarID: 100338

CAID:

gnomAD: 6.195e-7 (1 in 1614092) no homozygotes https://gnomad.broadinstitute.org/variant/12-6110483-A-G?dataset=gnomad_r4

MultipleGeneVariants:

VWF variant

Variant: c.7940C>T p.Thr2647Met p.Thr2647Met

ClinVarID: 100487

gnomAD: 0.004007 (6468 in 1614124) 21 homozygotes https://gnomad.broadinstitute.org/variant/12-5953542-G-A?dataset=gnomad_r4

Case UZ089: 17 year old female (row 90 in supplementary table)

DiseaseAssertion: type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370

CaseHPOFreeRext: vWF:Ag (%) = 17.7; vWF:GPIbR (%) = 14.2; Act/Ag ratio = 0.80; FVIII:C (%) = 49.8; Platelets (x10^9/L) = 242

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.3359G>C p.Trp1120Ser

HGVS:

ClinVarID: 100256

CAID:

gnomAD: 0.000001239 (2 in 1613892) no homozygotes https://gnomad.broadinstitute.org/variant/12-6023651-C-G?dataset=gnomad_r4

Case UZ009: 42 year old female (row 10 supplemental table)

DiseaseAssertion: type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: vWF:Ag (%) = 26.2; vWF:GPIbR (%) = 20.8; Act/Ag ratio = 0.79; FVIII:C (%) = 29.7; Platelets (x10^9/L) = 337

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.6859C>T p.Arg2287Trp

HGVS:

ClinVarID: 100450

CAID:

gnomAD: 0.0004764 (769 in 1614122) 3 homozygotes https://gnomad.broadinstitute.org/variant/12-5985605-G-A?dataset=gnomad_r4

Case 1: 0 y.o. female, study ID UZ083 in Supplemental table

DiseaseAssertion: type 1 VWD presequencing; type 2M VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370

CaseHPOFreeRext: vWF:Ag (%) = 17.7; vWF:GPIbR (%) = 14; Act/Ag ratio = 0.79; FVIII:C (%) = 44.5; Platelets (x10^9/L) = 323

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished: If applicable.

Gene: VWF

Variant: c.5087T>G p.Leu1696Arg

HGVS:

ClinVarID: 1684480

CAID:

gnomAD: absent

Case UZ041: 2 year old male

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370

CaseHPOFreeRext: vWF:Ag (%) = 9.9; vWF:GPIbR (%) = 5.7; Act/Ag ratio = 0.6; FVIII:C (%) = 19.9; Platelets (x10^9/L) = 352

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.3380-2A>G p.?

HGVS:

ClinVarID: 1684020

CAID:

gnomAD: absent

Case UZ071: 2 year old female (row 72 in supplemental table)

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440, HP:0040225

CaseHPOFreeRext: vWF:Ag (%) = 16.1; vWF:GPIbR (%) = 3.4; Act/Ag ratio = 0.21; FVIII:C (%) = 17; Platelets (x10^9/L) = 537

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4517C>T p.Ser1506Leu

HGVS:

ClinVarID: 100369

CAID:

gnomAD: absent

MultipleGeneVariants:

Gene: FGG

Variant: c.571G>A p.Gly191Arg

ClinVarID: 16378

gnomAD: 0.003866 (6239 in 1613896) 21 homozygotes https://gnomad.broadinstitute.org/variant/4-154609725-C-T?dataset=gnomad_r4

Case UZ043: 8 year old male (row 44 supplemental table)

DiseaseAssertion: type 2B VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 29.3; vWF:GPIbR (%) = 13.6; Act/Ag ratio = 0.46; FVIII:C (%) = 68.1; Platelets (x10^9/L) = 176

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4021C>T p.Arg1341Trp

HGVS:

ClinVarID: 100316

CAID:

gnomAD: 0.00001859 (30 in 1613842) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019397-G-A?dataset=gnomad_r4

Case UZ092: 28 year old female (row 93 in supplementary table)

DiseaseAssertion: type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 16; vWF:GPIbR (%) = 12; Act/Ag ratio = 0.75; FVIII:C (%) = 28; Platelets (x10^9/L) = 288

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4135C>T p.Arg1379Cys

HGVS:

ClinVarID: 100333

CAID:

gnomAD: 0.00002540 (41 in 1613910) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019283-G-A?dataset=gnomad_r4

MultipleGeneVariants:

Gene: F11

Variant: c.1305-2A>G

ClinVarID: 2572126

gnomAD: absent

Case 13: 40 year old male, study ID UZ094 in supplemental table

DiseaseAssertion: type 2 NOS VWD presequencing, type 2M VWD postsequencing

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442

CaseHPOFreeRext: vWF:Ag (%) = 61.2; vWF:GPIbR (%) = 24.8; Act/Ag ratio = 0.41; FVIII:C (%) = 31.5; Platelets (x10^9/L) = 368; normal multimers

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting: The Thrombosis-Hemostasis gene panel test used whole exome sequencing and included 99 diagnostic-grade genes (table 1 in PMID:36696193)

GenotypingMethod: WES using the coagulation subpanel of the UZ Leuven Thrombosis-Haemostasis gene panel test. WES was performed on the sequencing platform NovaSeq 6000 (Illumina), and Alissa Interpret software v5.2-5.4 (Agilent) was used for variant interpretation. Assessment of copy number variation was validated within the bioinformatics pipeline. The American College of Medical Genetics and Genomics and the Association of Molecular Pathology guidelines were used to classify variants as pathogenic (P), likely pathogenic (LP), a variant of uncertain significance (VUS), or (likely) benign (LB, B) variants

PreviouslyPublished:

Gene: VWF

Variant: c.4195C>T p.Arg1399Cys

HGVS:

ClinVarID: 100337

CAID:

gnomAD: 0.00005143 (83 in 1613776) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019223-G-A?dataset=gnomad_r4

Case: 3 (Also in row 1 table 6)

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = n/a; VWF:Ac [IU/dL] = 17; FVIII:C [IU/dL] = 15

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.1324C>T p.Arg442Cys

HGVS:

ClinVarID: 806808

CAID:

gnomAD: 0.00003098 (50 in 1614024) no homoztygotes https://gnomad.broadinstitute.org/variant/12-6064354-G-A?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.6536C>T p.Ser2179Phe

ClinVarID: 100442

gnomAD: 6.196e-7 (1 in 1614072) no homozygotes https://gnomad.broadinstitute.org/variant/12-5993924-G-A?dataset=gnomad_r4

Case: IP #28 (also in row 14 table 6)

DiseaseAssertion: type 2A VWF

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 39; VWF:Ac [IU/dL] = 7; FVIII:C [IU/dL] = 61

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4078G>T p.Val1360Phe

HGVS:

ClinVarID: 1809581

CAID:

gnomAD: absent

Case: IP #9

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 17; VWF:Ac [IU/dL] = 10; FVIII:C [IU/dL] = 51

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2771G>A p.Arg924Gln

HGVS:

ClinVarID: 100240

CAID:

gnomAD: 0.01774 (28642 in 1614096) 297 homozygotes https://gnomad.broadinstitute.org/variant/12-6031493-C-T?dataset=gnomad_r4

Case: IP #34

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 55; VWF:Ac [IU/dL] = 35; FVIII:C [IU/dL] = 60

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4517C>T p.Ser1506Leu

HGVS:

ClinVarID: 100369

CAID:

gnomAD: absent

Case: IP #26 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 50; VWF:Ac [IU/dL] = 29; FVIII:C [IU/dL] = 40

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3673T>G p.Cys1225Gly

HGVS:

ClinVarID: 100272

CAID:

gnomAD: absent

Case: IP #15 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = n/a; VWF:Ac [IU/dL] = 50; FVIII:C [IU/dL] = n/a; VWF:CB (IU/dL) = 25

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.5191T>A p.Ser1731Thr

HGVS:

ClinVarID: 100420

CAID:

gnomAD: 0.001158 (1870 in 1614210) 5 homozygotes https://gnomad.broadinstitute.org/variant/12-6016636-A-T?dataset=gnomad_r4

Case: IP #33 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 11; VWF:Ac [IU/dL] = 4; FVIII:C [IU/dL] = 10

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>A p.Arg1374Ser

HGVS:

ClinVarID: 100328

CAID:

gnomAD: absent

Case: IP #55

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 71; VWF:Ac [IU/dL] = 17; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4825G>A p.Gly1609Arg

HGVS:

ClinVarID: 100395

CAID:

gnomAD: 0.000003098 (5 in 1614130) no homozygotes https://gnomad.broadinstitute.org/variant/12-6018593-C-T?dataset=gnomad_r4

Case: IP #29 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 21; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 42

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #12 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2M/2B/1) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 7; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = 8

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3835G>A p.Val1279Ile

HGVS:

ClinVarID: 100288

CAID:

gnomAD: 0.0003751 (605 in 1612942) 1 homozygote https://gnomad.broadinstitute.org/variant/12-6019583-C-T?dataset=gnomad_r4

Case: IP #25 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 22; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 26

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #9 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440 - blood group B

CaseHPOFreeRext: VWF:Ag [IU/dL] = 91; VWF:Ac [IU/dL] = 28; FVIII:C [IU/dL] = 105; VWF:CB (IU/dL) = 88

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4195C>T p.Arg1399Cys

HGVS:

ClinVarID: 100337

CAID:

gnomAD: 0.00005143 (83 in 1613776) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019223-G-A?dataset=gnomad_r4

Case: IP #4 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 37; VWF:Ac [IU/dL] = 41; FVIII:C [IU/dL] = 36

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2278C>T p.Arg760Cys

HGVS:

ClinVarID: 100208

CAID:

gnomAD: 0.000006196 (10 in 1614050) no homozygotes https://gnomad.broadinstitute.org/variant/12-6046726-G-A?dataset=gnomad_r4

Case: IP #11 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 21; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 32; VWF:CB (IU/dL) = 14

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4225G>T p.Val1409Phe

HGVS:

ClinVarID: 3393378

CAID:

gnomAD: absent

Case: IP #36 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 42; VWF:Ac [IU/dL] = 15; FVIII:C [IU/dL] = 53

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4241T>G p.Val1414Gly

HGVS:

ClinVarID: 619752

CAID:

gnomAD: absent

Case: 9

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 80; VWF:Ac [IU/dL] = 26; FVIII:C [IU/dL] = 118

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2771G>A p.Arg924Gln

HGVS:

ClinVarID: 100240

CAID:

gnomAD: 0.01774 (28642 in 1614096) 297 homozygotes https://gnomad.broadinstitute.org/variant/12-6031493-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.4789C>T Arg1597Trp

ClinVarID: 285

Case: IP #14 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 94; VWF:Ac [IU/dL] = 89; FVIII:C [IU/dL] = 126; VWF:CB (IU/dL) = 49

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.5191T>A p.Ser1731Thr

HGVS:

ClinVarID: 100420

CAID:

gnomAD: 0.001158 (1870 in 1614210) 5 homozygotes https://gnomad.broadinstitute.org/variant/12-6016636-A-T?dataset=gnomad_r4

Case: IP #64

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 34; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 42

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4892G>A p.Gly1631Asp

HGVS:

ClinVarID: 1342155

CAID:

gnomAD: absent

Case: IP #32 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 11; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 17

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>A p.Arg1374Ser

HGVS:

ClinVarID: 100328

CAID:

gnomAD: absent

Case: IP #4 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/1) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 14; VWF:Ac [IU/dL] = 14; FVIII:C [IU/dL] = 23

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3389G>A p.Cys1130Tyr

HGVS:

ClinVarID: 1684001

CAID:

gnomAD: absent

Case: IP #3 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 52; VWF:Ac [IU/dL] = 41; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2278C>T p.Arg760Cys

HGVS:

ClinVarID: 100208

CAID:

gnomAD: 0.000006196 (10 in 1614050) no homozygotes https://gnomad.broadinstitute.org/variant/12-6046726-G-A?dataset=gnomad_r4

Case: IP #24 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 22; VWF:Ac [IU/dL] = 10; FVIII:C [IU/dL] = 40

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #35 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032441 - blood group AB

CaseHPOFreeRext: VWF:Ag [IU/dL] = 14; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 30

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4241T>G p.Val1414Gly

HGVS:

ClinVarID: 619752

CAID:

gnomAD: absent

Case: IP #12 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 23; VWF:Ac [IU/dL] = 21; FVIII:C [IU/dL] = 52; VWF:CB (IU/dL) = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.5191T>A p.Ser1731Thr

HGVS:

ClinVarID: 100420

CAID:

gnomAD: 0.001158 (1870 in 1614210) 5 homozygotes https://gnomad.broadinstitute.org/variant/12-6016636-A-T?dataset=gnomad_r4

Case: IP #28 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 11; VWF:Ac [IU/dL] = 4; FVIII:C [IU/dL] = 11

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #1

DiseaseAssertion: type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 11.4; VWF:Ac [IU/dL] = 4; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.421G>A p.Asp141Asn

HGVS:

ClinVarID: 100338

CAID:

gnomAD: absent

Case: IP #3 (also in row 1 splice variants table 6)

DiseaseAssertion: Type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 49; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.1110-6_1110-5insC

HGVS: NM_000552.5:c.1110-6dup p.?

ClinVarID: 507028

CAID:

gnomAD: absent

Case: IP #4

DiseaseAssertion: type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 117; VWF:Ac [IU/dL] = 52; FVIII:C [IU/dL] = 104

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.1309_1326del p.Asp437_Arg442del

HGVS:

ClinVarID: 100179

CAID:

gnomAD: 0.000001239 (2 in 1614154) no homozygotes https://gnomad.broadinstitute.org/variant/12-6064351-AGCGGGTGCACACAGCGTC-A?dataset=gnomad_r4

Case: IP #15

DiseaseAssertion: type 2A (IIE) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 41; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = 82

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3390C>T p.Cys1130Cys

HGVS:

ClinVarID: 627186

CAID:

gnomAD: 0.000006021 (3 in 498246) no homozygotes https://gnomad.broadinstitute.org/variant/12-6022888-G-A?dataset=gnomad_r4

Case: IP #39

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 110; VWF:Ac [IU/dL] = 14; FVIII:C [IU/dL] = 103

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4645G>A p.Glu1549Lys

HGVS:

ClinVarID: 100379

CAID:

gnomAD: absent

Case: IP #13 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 47; VWF:Ac [IU/dL] = 46; FVIII:C [IU/dL] = 86; VWF:CB (IU/dL) = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.5191T>A p.Ser1731Thr

HGVS:

ClinVarID: 100420

CAID:

gnomAD: 0.001158 (1870 in 1614210) 5 homozygotes https://gnomad.broadinstitute.org/variant/12-6016636-A-T?dataset=gnomad_r4

Case: IP #57

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 53; VWF:Ac [IU/dL] = 15; FVIII:C [IU/dL] = 46

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4825G>A p.Gly1609Arg

HGVS:

ClinVarID: 100395

CAID:

gnomAD: 0.000003098 (5 in 1614130) no homozygotes https://gnomad.broadinstitute.org/variant/12-6018593-C-T?dataset=gnomad_r4

Case: IP #1 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 37; VWF:Ac [IU/dL] = 36; FVIII:C [IU/dL] = 46

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.-411T>C

HGVS:

ClinVarID: not found

CAID: not found

gnomAD: absent

**MultipleGeneVariants:

Gene: VWF

Variant: c.+167G>T

Gene: VWF

Variant: c.2278C>T p.Arg760Cys

ClinVarID: 100208

gnomAD: 0.000006196 (10 in 1614050) no homozygotes https://gnomad.broadinstitute.org/variant/12-6046726-G-A?dataset=gnomad_r4

Case: IP #24 in type 2B VWD sub-cohort

DiseaseAssertion: type 2B VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 19; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: 0.000003098 (5 in 1613796) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019298-G-A?dataset=gnomad_r4

Case: IP #2 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 17; VWF:Ac [IU/dL] = 15; FVIII:C [IU/dL] = 18

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2625C>T p.Tyr875=

HGVS:

ClinVarID: 439330

CAID:

gnomAD: 0.000003717 (6 in 1614106) no homozygotes https://gnomad.broadinstitute.org/variant/12-6034748-G-A?dataset=gnomad_r4

Case: IP #2

DiseaseAssertion: type 2A (IIC) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 201; VWF:Ac [IU/dL] = 124; FVIII:C [IU/dL] = 244

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.1309_1326del p.Asp437_Arg442del

HGVS:

ClinVarID: 100179

CAID:

gnomAD: 0.000001239 (2 in 1614154) no homozygotes https://gnomad.broadinstitute.org/variant/12-6064351-AGCGGGTGCACACAGCGTC-A?dataset=gnomad_r4

Case: IP #11 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 18; VWF:Ac [IU/dL] = 12; FVIII:C [IU/dL] = 27

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3586T>C p.Cys1196Arg

HGVS:

ClinVarID: 100270

CAID:

gnomAD: 0.000001239 (2 in 1614220) no homozygotes https://gnomad.broadinstitute.org/variant/12-6021988-A-G?dataset=gnomad_r4

Case: IP #63

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440 - blood group B

CaseHPOFreeRext: VWF:Ag [IU/dL] = 45; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 36

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4885G>A p.Gly1629Arg

HGVS:

ClinVarID: 100398

CAID:

gnomAD: absent

Case: IP #8 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 30; VWF:Ac [IU/dL] = 16; FVIII:C [IU/dL] = 61; VWF:CB (IU/dL) = 43

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4105T>A p.Phe1369Ile

HGVS:

ClinVarID: 100326

CAID:

gnomAD: 0.000006197 (10 in 1613726) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019313-A-T?dataset=gnomad_r4

Case: IP #38 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2B) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 19; VWF:Ac [IU/dL] = 1; FVIII:C [IU/dL] = 27

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4373G>A p.Cys1458Tyr

HGVS:

ClinVarID: 100351

CAID:

gnomAD: absent

Case: IP #5 in type U VWD sub-cohort (also in row 3 splice variants table 6)

DiseaseAssertion: unclassified (2A/1) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 17; VWF:Ac [IU/dL] = 16; FVIII:C [IU/dL] = 20

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3389G>A

HGVS:

ClinVarID: 1684001

CAID:

gnomAD: absent

MultipleGeneVariants:

Gene: VWF

Variant: c.3539–10T>G

ClinVarID: not found

**gnomAD: absent

Case: IP #31 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 32; VWF:Ac [IU/dL] = 14; FVIII:C [IU/dL] = 43

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #34 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 19; VWF:Ac [IU/dL] = 6; FVIII:C [IU/dL] = 38

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4121G>A p.Arg1374His

HGVS:

ClinVarID: 100330

CAID:

gnomAD: 0.000001239 (2 in 1613878) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019297-C-T?dataset=gnomad_r4

Case: IP #3 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 13; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 22

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2771G>A p.Arg924Gln

HGVS:

ClinVarID: 100240

CAID:

gnomAD: 0.01774 (28642 in 1614096) 297 homozygotes https://gnomad.broadinstitute.org/variant/12-6031493-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.3943C>T p.Arg1315Cys

**ClinVarID: 100310

gnomAD: 6.196e-7 (1 in 1613892) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019475-G-A?dataset=gnomad_r4

Case: IP #27 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 18; VWF:Ac [IU/dL] = 12; FVIII:C [IU/dL] = 22

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #2 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440 - blood group B

CaseHPOFreeRext: VWF:Ag [IU/dL] = 43; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = 10

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.1117C>T p.Arg373*

HGVS:

ClinVarID: 100175

CAID:

gnomAD: 0.000008055 (13 in 1614004) no homozygotes https://gnomad.broadinstitute.org/variant/12-6071336-G-A?dataset=gnomad_r4

**MultipleGeneVariants:

Gene: VWF

Variant: c.2561G>A p.Arg854Gln

ClinVarID: 296

gnomAD: 0.004956 (8000 in 1614214) 26 homozygotes https://gnomad.broadinstitute.org/variant/12-6034812-C-T?dataset=gnomad_r4

Case: IP #35

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 65; VWF:Ac [IU/dL] = 10; FVIII:C [IU/dL] = 24

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4517C>T p.Ser1506Leu

HGVS:

ClinVarID: 100369

CAID:

gnomAD: absent

Case: IP #56

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440 - blood group B

CaseHPOFreeRext: VWF:Ag [IU/dL] = 46; VWF:Ac [IU/dL] = 12; FVIII:C [IU/dL] = 60

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4825G>A p.Gly1609Arg

HGVS:

ClinVarID: 100395

CAID:

gnomAD: 0.000003098 (5 in 1614130) no homozygotes https://gnomad.broadinstitute.org/variant/12-6018593-C-T?dataset=gnomad_r4

Case: IP #27 in type 2N VWD sub-cohort

DiseaseAssertion: type 2N VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 42; VWF:Ac [IU/dL] = 44; FVIII:C [IU/dL] = 69

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3673T>G p.Cys1225Gly

HGVS:

ClinVarID: 100272

CAID:

gnomAD: absent

Case: IP #40

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 46; VWF:Ac [IU/dL] = 31; FVIII:C [IU/dL] = 57

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4690C>T p.Arg1564Trp

HGVS:

ClinVarID: 811702

CAID:

gnomAD: 0.000006818 (11 in 1613330) no homozygotes https://gnomad.broadinstitute.org/variant/12-6018728-G-A?dataset=gnomad_r4

Case: IP #23

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 19; VWF:Ac [IU/dL] = 9; FVIII:C [IU/dL] = 37

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3686T>G p.Val1229Gly

HGVS:

ClinVarID: 100274

CAID:

gnomAD: 0.002237 (3603 in 1610354) 17 homozygotes https://gnomad.broadinstitute.org/variant/12-6019732-A-C?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.3692A>C p.Asn1231Thr

ClinVarID: 100275

gnomAD:

Case: IP #26 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 23; VWF:Ac [IU/dL] = 6; FVIII:C [IU/dL] = 23

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #30 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M/1C) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 20; VWF:Ac [IU/dL] = 11; FVIII:C [IU/dL] = 27

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4120C>T p.Arg1374Cys

HGVS:

ClinVarID: 100329

CAID:

gnomAD: absent

Case: IP #24 in type 2N VWD sub-cohort (also in row 5 splice variants table 6)

DiseaseAssertion: type 2N/1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032441 - blood group AB

CaseHPOFreeRext: VWF:Ag [IU/dL] = 42; VWF:Ac [IU/dL] = 34; FVIII:C [IU/dL] = 16

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.2561G>A p.Arg854Gln

HGVS:

ClinVarID: 296

CAID:

gnomAD: 0.004956 (8000 in 1614214) 26 homozygotes https://gnomad.broadinstitute.org/variant/12-6034812-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.6798+2T>A

ClinVarID: 1803122

gnomAD: absent

Case: IP #13 (also in row 7 table 6)

DiseaseAssertion: type 2A (IIE) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 23; VWF:Ac [IU/dL] = n/a; FVIII:C [IU/dL] = 45

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3314C>A p.Ala1105Asp

HGVS:

ClinVarID: 626953

CAID:

gnomAD: absent

Case: IP #67

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 9,3; VWF:Ac [IU/dL] = 4; FVIII:C [IU/dL] = 41

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.7988G>C p.Arg2663Pro

HGVS:

ClinVarID: 372760

CAID:

gnomAD: 0.001352 (2181 in 1613616) 4 homozygotes https://gnomad.broadinstitute.org/variant/12-5952518-C-G?dataset=gnomad_r4

Case: IP #22 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 34; VWF:Ac [IU/dL] = 27; FVIII:C [IU/dL] = 95

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4022G>A p.Arg1341Gln

HGVS:

ClinVarID: 291

CAID:

gnomAD: 0.000001239 (2 in 1613944) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019396-C-T?dataset=gnomad_r4

MultipleGeneVariants:

Gene: VWF

Variant: c.5801T>G p.Val1934Gly

ClinVarID: 627336

gnomAD: 0.00006260 (101 in 1613356) no homozygotes https://gnomad.broadinstitute.org/variant/12-6011658-A-C?dataset=gnomad_r4

Case: 2

DiseaseAssertion: type 2A VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 14; VWF:Ac [IU/dL] = 8; FVIII:C [IU/dL] = 34

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.-2522C>T

HGVS:

ClinVarID: not found

CAID: not found

gnomAD:

MultipleGeneVariants:

Gene: VWF

Variant: c.3586T>C

ClinVarID: 100270

Case: IP #65

DiseaseAssertion: type 2A (IIA) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: VWF:Ag [IU/dL] = 33; VWF:Ac [IU/dL] = 15; FVIII:C [IU/dL] = n/a

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4912G>A p.Glu1638Lys

HGVS:

ClinVarID: 100403

CAID:

gnomAD: absent

Case: IP #37 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/2M) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 15; VWF:Ac [IU/dL] = 7; FVIII:C [IU/dL] = 25

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4241T>G p.Val1414Gly

HGVS:

ClinVarID: 619752

CAID:

gnomAD: absent

Case: IP #10 in type 2M VWD sub-cohort

DiseaseAssertion: type 2M VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032440 - blood group B

CaseHPOFreeRext: VWF:Ag [IU/dL] = 73; VWF:Ac [IU/dL] = 23; FVIII:C [IU/dL] = 79; VWF:CB (IU/dL) = 57

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4195C>T p.Arg1399Cys

HGVS:

ClinVarID: 100337

CAID:

gnomAD: 0.00005143 (83 in 1613776) no homozygotes https://gnomad.broadinstitute.org/variant/12-6019223-G-A?dataset=gnomad_r4

Case: IP #23 in type U VWD sub-cohort

DiseaseAssertion: unclassified (2A/1/M) VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032442 - blood group O

CaseHPOFreeRext: VWF:Ag [IU/dL] = 12; VWF:Ac [IU/dL] = 4; FVIII:C [IU/dL] = 14

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.4094T>C p.Leu1365Pro

HGVS:

ClinVarID: 2438545

CAID:

gnomAD: absent

Case: IP #10 in type U VWD sub-cohort

DiseaseAssertion: unclassified VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: HP:0032370 - blood group A

CaseHPOFreeRext: VWF:Ag [IU/dL] = 21; VWF:Ac [IU/dL] = 18; FVIII:C [IU/dL] = 55

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Sequence variations in the VWF were identified through direct sequencing, while the detection of large rearrangements utilized the multiplex ligation-dependent probe amplification (MLPA) technique or assessed copy number variations (CNVs). Sanger sequencing methodology was applied for VWF analysis in patients investigated prior to 2016 (approximately 14% of IPs), whereas next-generation sequencing (NGS) was employed for the analysis of VWF in patients inspected from 2017 onwards (about 86% of IPs). In both strategies, the entire VWF, encompassing all 52 exons, intron/exon boundaries, and promoter regions, was analyzed.

PreviouslyPublished:

Gene: VWF

Variant: c.3586T>C p.Cys1196Arg

HGVS:

ClinVarID: 100270

CAID:

gnomAD: 0.000001239 (2 in 1614220) no homozygotes https://gnomad.broadinstitute.org/variant/12-6021988-A-G?dataset=gnomad_r4

Case: Case 2, male, newborn

DiseaseAssertion: VWD2B

FamilyInfo: First child of consanguineous parents (first cousins), no family history of bleeding, search of maternal platelet autoantibodies was negative; parents had VWF measurements showed decreased VWF:RCo, ratio FVIII:C/VWF:Ag < 0.5, and enhanced RIPA

ParentalGenotype(s): both parents heterozygous for both variants

CasePresentingHPOs: HP:0012330, HP:0001873, HP:0000967, HP:0030129

(Pyelonephritis, thrombocytopenia, petechiae, impaired ristocetin cofactor assay activity)

CaseHPOFreeText: born at 40wks, thrombocytopenia: 5 GL−1 at birth, platelets clumps in citrate tube, normal platelet morphology, no platelet incompatibility between the mother and the child in HPA groups 1, 3, 5, and 15, Allo- and autoantibodies on the mother and child and cross-match between father and mother serum were negative; bone marrow aspiration showed hyperplasia of megakaryocyte line, with all stages of maturation, consistent with peripheral origin, normal development; VWF:RCo = 13 IU dL−1, VWF:Ag = 47 IU dL−1, VWF:RCo /VWF:Ag= 0.3, FVIII:C = 22 IU dL−1, FVIII/VWF:Ag= 0.6, VWF:FVIII = 10 IU dL−1< RIPA analysis could not be performed

CaseNOTHPOs: HP:0032169, HP:0001892

(infection, abnormal bleeding)

CaseNOTHPOFreeText: DIC

CasePreviousTesting: NA

GenotypingMethod: Sequencing of exon 20 and 28 of VWF gene

PreviouslyPublished: NA

Gene: VWF

Variant 1: c.4010C>T (p.Pro1337Leu); exon 28, homozygous

HGVS: NM_000552.4(VWF):c.4010C>T (p.Pro1337Leu)

ClinVarID: 100314; https://www.ncbi.nlm.nih.gov/clinvar/variation/100314/

CAID: NA

gnomAD: MAF = 0.00005440 (1/18384 alleles) in East Asian population; https://gnomad.broadinstitute.org/variant/12-6128574-G-A?dataset=gnomad_r2_1

Variant 2: c.2561G>A (p.Arg854Gln); exon 20; homozygous

HGVS: NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)

ClinVarID: 296; https://www.ncbi.nlm.nih.gov/clinvar/variation/296/

CAID: NA

gnomAD: MAF = 0.005692 (143/25122 alleles, 4 homozygotes) in European (non-Finnish) population; https://gnomad.broadinstitute.org/variant/12-6143978-C-T?dataset=gnomad_r2_1

Case: T1-4, male, 64yo

DiseaseAssertion: VWD1

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeText: Blood type: unknown, bleeding score = 12, VWF:Ag (IU/mL) = 0.44; VWF:RCo (IU/mL) = 0.44; FVIII:C (IU/mL) = 0.75

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: qRT-PCR

PreviouslyPublished:

Gene: VWF

Variant: c.6599-20A>T

HGVS: NM_000552.5(VWF):c.6599-20A>T

ClinVarID: 100444; https://www.ncbi.nlm.nih.gov/clinvar/variation/100444/?oq=c.6599-20A%3ET&m=NM_000552.5(VWF):c.6599-20A%3ET

CAID:

gnomAD: MAF = 0.0002795 (other population)

Case: T3-5, female, 19yo

DiseaseAssertion: VWD3

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs: