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: Proband 1 (Family 1)

DiseaseAssertion: VWD1

FamilyInfo: 2 family members diagnosed with VWD1

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147, HP:0001892, HP:0030130

(Reduced quantity of Von Willebrand factor, Abnormal bleeding, Impaired von Willibrand factor collagen binding activity)

CaseHPOFreeText: normal to slightly prolonged Ivy BT, FVIII:C % = 28, VWF:Ag % = 12, VWF:RCo % = 14, VIII C/vWF:AG ratio = 2.3, vWF:Rco/vWF:AG ratio = 1.2

CaseNOTHPOs: HP:0011871, HP:0030132

(Impaired ristocetin-induced platelet aggregation, Absence of large von Willibrand factor multimers)

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NA

PreviouslyPublished: PMID: 11992235

Gene: VWF

Variant: c.6536C>T (p.Ser2179Phe)

HGVS: NM_000552.4(VWF):c.6536C>T (p.Ser2179Phe)

ClinVarID: 100442; https://www.ncbi.nlm.nih.gov/clinvar/variation/100442/

CAID:

gnomAD: absent

Case: Proband 3 (S2179F)

DiseaseAssertion: VWD1

FamilyInfo: NA

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147, HP:0001892, HP:0030130

(Reduced quantity of Von Willebrand factor, Abnormal bleeding, Impaired von Willibrand factor collagen binding activity)

CaseHPOFreeText: normal to slightly prolonged Ivy BT, FVIII:C % = 26, VWF:Ag % = 6, VWF:RCo % = 6, VIII C/vWF:AG ratio = 4.3, vWF:Rco/vWF:AG ratio = 1.0

CaseNOTHPOs: HP:0011871, HP:0030132

(Impaired ristocetin-induced platelet aggregation, Absence of large von Willibrand factor multimers)

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NA

PreviouslyPublished: PMID: 11992235

Gene: VWF

Variant: c.6536C>T (p.Ser2179Phe)

HGVS: NM_000552.4(VWF):c.6536C>T (p.Ser2179Phe)

ClinVarID: 100442; https://www.ncbi.nlm.nih.gov/clinvar/variation/100442/

CAID:

gnomAD: absent

Case: Proband 2 (Family 2)

DiseaseAssertion: VWD1

FamilyInfo: 2 family members diagnosed with VWD1

ParentalGenotype(s): NA

CasePresentingHPOs: HP:0012147, HP:0001892, HP:0030130, HP:0011871

(Reduced quantity of Von Willebrand factor, Abnormal bleeding, Impaired von Willibrand factor collagen binding activity)

CaseHPOFreeText: normal to slightly prolonged Ivy BT, FVIII:C % = 19, VWF:Ag % = 13, VWF:RCo % = 12, VIII C/vWF:AG ratio = 1.5, vWF:Rco/vWF:AG ratio = 0.9

CaseNOTHPOs: HP:0030132

(Absence of large von Willibrand factor multimers)

CaseNOTHPOFreeText:

CasePreviousTesting: NA

GenotypingMethod: NA

PreviouslyPublished: PMID: 11992235

Gene: VWF

Variant: c.6536C>T (p.Ser2179Phe)

HGVS: NM_000552.4(VWF):c.6536C>T (p.Ser2179Phe)

ClinVarID: 100442; https://www.ncbi.nlm.nih.gov/clinvar/variation/100442/

CAID:

gnomAD: absent