Case: Row 2 in Supplemental Table 1. Represents 1 patient that has two variants in VWF.

DiseaseAssertion: type 3 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: FVIII:C/VWF:Ag = 3.0 (1.7-4.0); VWFpp/VWF:Ag = 1.9 (1.5-2.9)

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Genetic analysis was performed at the laboratory of hematology of the Radboud University Medical Center in Nijmegen. Ion semiconductor sequencing (Ion-Torrent) was used to analyze the VWF gene from peripheral blood obtained in EDTA tubes or from saliva samples. The 52 exons of VWF gene were analyzed including ±20 bp exon-intron boundaries. If no VWF gene variant was detected, multiplex ligation-dependent probe amplification (MLPA) analysis was performed to find large deletions or duplications. Thus, MLPA was performed in 183 patients (46.9%). All variants were confirmed with Sanger sequencing.

PreviouslyPublished:

Gene: VWF

Variant: Del exon 4-5

HGVS: c.221-977_532+7059del

ClinVarID: 156329

CAID:

gnomAD: absent

MultipleVariants:

Gene: VWF

Variant: L2306R fs*4

Case: Row 2 in Supplemental Table 1. Represents 13 patients in 13 families.

DiseaseAssertion: 13 type 1 VWD

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeRext: FVIII:C/VWF:Ag = 3.0 (1.7-4.0); VWFpp/VWF:Ag = 1.9 (1.5-2.9)

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: Genetic analysis was performed at the laboratory of hematology of the Radboud University Medical Center in Nijmegen. Ion semiconductor sequencing (Ion-Torrent) was used to analyze the VWF gene from peripheral blood obtained in EDTA tubes or from saliva samples. The 52 exons of VWF gene were analyzed including ±20 bp exon-intron boundaries. If no VWF gene variant was detected, multiplex ligation-dependent probe amplification (MLPA) analysis was performed to find large deletions or duplications. Thus, MLPA was performed in 183 patients (46.9%). All variants were confirmed with Sanger sequencing.

PreviouslyPublished:

Gene: VWF

Variant: Del exon 4-5

HGVS: c.221-977_532+7059del

ClinVarID: 156329

CAID:

gnomAD: absent

Case: T1-2, female, 52yo

DiseaseAssertion: VWD1

FamilyInfo:

ParentalGenotype(s):

CasePresentingHPOs:

CaseHPOFreeText: Blood type: O+, bleeding score = 12, VWF:Ag (IU/mL) = 0.14; VWF:RCo (IU/mL) = 0.13; FVIII:C (IU/mL) = 0.46

CaseNOTHPOs:

CaseNOTHPOFreeText:

CasePreviousTesting:

GenotypingMethod: qRT-PCR

PreviouslyPublished:

Gene: VWF

Variant: c.221-977_532+7059del

HGVS: NM_000552.5(VWF):c.221-977_532+7059del

ClinVarID: 156329; https://www.ncbi.nlm.nih.gov/clinvar/variation/156329/?oq=c.221-977_532+7059del&m=NM_000552.5(VWF):c.221-977_532%207059del

CAID: n/a

gnomAD: absent