Case#: 07003, Age 29, Female, Blood Type O+ (Table S3)

Disease Assertion: VWD1

FamilyInfo: The patient is the only member of Family#0703.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: VWF:Ag: 25, VWF:RCo:24.9, FVIII:C: 50, VWF:CB:28

CaseNotHPOs: N/A

CaseNotHPOFreeText: Bleeding Score 5

Protein Expression: N/A

CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations

Gene: VWF

Variant:NM_000552.4:c.5170+10C>T and NM_000552.4:c.8254-5T>G

ClinVar: 100418 ClinVar1

CAID: CA228702 and CA923726359 CAID1 CAID2

gnomAD: MAF of 0.01298 (326/ 25116 alleles) in the European (Finnish) population (CA228702).

gnomAD1

Case#: 22001, Age 41, Female, Blood Type O+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is the only member of Family# 2201.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 14, VWF:Ag:18, VWF:RCo:17.5, FVIII:C: 35, VWF:CB: 17

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Protein Expression: N/A

CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations

Gene: VWF

Variant: NM_000552.4:c.5170+10C>T (p.=) and NM_000552.4(VWF):c.7730-1G>C (p.=)

ClinVar: 100418 and 100485 ClinVar1 ClinVar2

CAID: CA228702 and CA228816 CAID1 CAID2

gnomAD: 0.01298 (326/25116 alleles) in the European (Finnish) population. (CA228702) gnomAD

Case#: 36001, Age 5, Male, Blood Type A+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is the only member of Family#3601.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: VWF:Ag: 33, VWF:RCo: 26.4, FVIII:C: 88, VWF:CB: 58

CaseNotHPOs: N/A

CaseNotHPOFreeText: Bleeding Score 2

Protein Expression: N/A

CasePreviousTesting: 48,48 Access-Array amplification. NGS Molecular analysis was performed. Sanger sequencing was used to validate selected mutations.

Gene: VWF

Variant: NM_000552.4(VWF):c.5170+10C>T (p.=) and NM_000552.4(VWF):c.7730-1G>C (p.=)

ClinVar: 100418 and 100485 ClinVar1 ClinVar2

CAID: CA228702 and CA228816 CAID1 CAID2

gnomAD: MAF of 0.01298 (326/ 25116 alleles) in the European (Finnish) population (CA228702). gnomAD

Case: 7 , F, 36, Italian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no

ParentalGenotype:

2435delC on the maternal allele

5170+10C→T on the paternal allele

253T→C on the paternal allele

CasePresentingHPOs: n/a

CaseHPOFreeText: VWF:Ag (U/dl): <1, Bleeding symptoms: Severe

CaseNotHPOs: n/a

CaseNotHPOFreeText: Anti-VWF alloantibodies: no

CasePreviousTesting: n/a

Gene: VWF

Variant:

2435delC (FS), Exon 18

5170+10C→T (Intronic), Exon 29

253T→C (Ser85Pro), Exon 4

Compound Heterozygous

Note: Article assumes that 5170+10C→T would be a frameshift mutation. No potential splice site mutation was confirmed at the mRNA level; “Splice Site Prediction program” found all mutations likely to disrupt normal splicing. No possible splice site mutation could be identified on 100 chromosomes from a group of 50 normal subjects with same genetic background as patients, excluding the possibility that these mutations represent common polymorphisms.