Case#: 23015, Age 74, Male, Blood Type A+ (Table S3)

Disease Assertion: VWD1

FamilyInfo: The patient is the only member of Family# 2310.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText:VWF:Ag: 18, VWF:RCo:17.3, FVIII:C:19, VWF:CB:13

CaseNotHPOs: N/A

CaseNotHPOFreeText: Bleeding Score 3

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.2546+132G>A(p.=) and NM_000552.4:c.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA232299449 and CA114160 CAID1 CAID2

gnomAD: MAF of 0.001179 ( 1/848 alleles) in the Latino population (CA232299449). gnomAD

Case#: 02023, Age 28, Female, Blood type O+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: Family# 0206. 3 family members were included in the study. Everyone in the family have the same variant and all have type 1 VWD.

Parental Genotype: Not listed

CasePresentingHPOs:

CaseHPOFreeText: Bleeding score 18, VWF:Ag: 5.5, VWF:RCo: 8, FVIII:C: 11, VWF:CB: 4.2

CaseNotHPOs:

CaseNotHPOFreeText:

Protein Expression:

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 05008, Age 30, Male, Blood Type A+ (Table S3)

Disease Assertion: VWD1

FamilyInfo: Patient is the only member of Family #0507

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 2, VWF:Ag: 5.8, VWF:RCo:5, FVIII:C: 7.4, VWF:CB:6.1

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 02059, Age 38, Male, Blood type A+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: Patient is a member of family # 02059. There is one other member of the family (patient 02060). 02060 has the same exonic variant (c.3614G>A), but has a different intronic variant ( c.7438-169G>A).

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding score 12, VWF:Ag: 5.4, VWF:RCo: 6.1, FVIII:C:11, VWF:CB: 4.5

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.3614G>A (p.Arg1205His) and

ClinVar: 308 ClinVar

CAID: CA114160 CAID1

gnomAD:

Case#: 02001, Age 63, Female, Blood Type A+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo:( Family 0201) 8 family members were included in the study. All of them had type VWD type 1. All had the same variant besides patient 02019.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 14, VWF:Ag: 9.7, VWF:RCo: 2.6, FVIII:C: 19, VWF:CB: 6

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160

CAID

gnomAD: N/A

Case#: 13006, Age 66, Male, Blood Type A-

Disease Assertion: VWD 1

FamilyInfo: The patient is the only member of Family# 1304.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 8, VWF:Ag:10, VWF:RCo: 6, FVIII:C:16, VWF:CB:6.1

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 37006, Age 45, Female, Blood Type B+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is the only member of Family#3706.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: VWF:Ag:7.6, VWF:RCo:5, FVIII:C: 8.9, VWF:CB: 6.9

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.3426T>C (p.Cys1142=), NM_000552.4:c.3614G>A (p.Arg1205His), NM_000552.4:c.7771-49G>A , NM_000552.4:c.3485_3486delinsTG (pPro1162Leu)

ClinVar: 256668 , 308, 619934 ClinVar1 ClinVar2 ClinVar3

CAID: CA6402757, CA114160, CA1139532197, and CA658683073 CAID1 CAID2 CAID3 CAID4

gnomAD: MAF of 0.2228 (2240/ 10052 alleles) in the African population (CA6402757). gnomAD

Case#: 10003, Age 33, Male, Blood Type A+ (Table S3)

Disease Assertion: VWD1

FamilyInfo: The patient and one other patient are members of Family#1002. The second member has the same exonic variant and also has an intronic variant.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 1, VWF:Ag:7.4, VWF:RCo: 7.2, FVIII:C:11, VWF:CB: 6.3

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 13012, Age 42, Male, Blood Type A+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is the only member of Family#1309.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding score 7, VWF:Ag:14, VWF:RCo:9, FVIII:C: 20, VWF:CB:11

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.3614G>A (p.Arg1205His) and

ClinVar: 308 ClinVar

CAID: CA114160 and CA6403769 CAID1 CAID2

gnomAD: MAF of 0.0005784 (20/34578 alleles) in the Latino population (CA6403769). gnomAD

Case#: 35003, Age 75, Female, Blood Type A- (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is one of two members in Family# 3502.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: VWF:Ag: 6.6, VWF:RCo: 8.5, FVIII:C:13, VWF:CB: 11

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:c.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 02064, Age 32, Male, Blood type O- (Table S3)

Disease Assertion: VWD 1

FamilyInfo: Patient is a part of family # 0224. There are 3 other members of the family (02065, 02066, 02067). All members of the family have the same variant.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding score 13, VWF:Ag: 4.7, VWF:RCo: 5, FVIII:C: 16, VWF:CB:6

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.3614G>A (p.Arg1205His)

ClinVar: 308

ClinVar

CAID: CA114160

CAID1

gnomAD: N/A

Case#: 02058, Age 64, Female, Blood type A+ (Table S3)

Disease Assertion: VWD1

FamilyInfo: Patient is the only member of family #0221.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding score 19, VWF:Ag: 7.3, VWF:RCo: 5.9, FVIII:C: 19, VWF:CB: 6.3

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.3614G>A (p.Arg1205His)

ClinVar: 308 ClinVar

CAID: CA114160 CAID

gnomAD: N/A

Case#: 18001, Age 50, Male, Blood Type B+ (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient one of 3 members of Family#1801. All of the patients have the same variant.

Parental Genotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: VWF:Ag:10, VWF:RCo:6.1, FVIII:C:17, VWF:CB:8.2

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.3614G>A (p.Arg1205His) and NM_000552.4:c.6989T>G (p.Val2330Gly)

ClinVar: 308 ClinVar1

CAID: CA114160 and CA6401808 CAID1 CAID2

gnomAD: MAF of 0.000008823 (1/113342 alleles) in the European (non-Finnish population) (CA6401808) gnomAD

Case: P9, M/26

DiseaseAssertion: VWD1

FamilyInfo: No family history

ParentalGenotype: NA

CaseHPOFreeText: The bleeding score was 1, aPTT was 44 seconds, FVIII:C was 9%, VWF:RCo was 13 IU/dL, and VWF:Ag was 6 IU/dL, with a VWF:RCo/VWF:Ag ratio of 2.0. The VWF multimer pattern was normal, RIPA was 3 ohms, and the platelet count was 217 × 10⁹/L.

CasePreviousTesting: NA

GenotypingMethod: Direct sequencing of all exons, flanking intronic sequences, and the promoter of VWF was performed.

Gene: VWF

Variant: c.3614G>A, p.R1205H — heterozygous

HGVS: NM_000552.5(VWF):c.3614G>A (p.Arg1205His)

ClinVar: 308

CAID: CA114160

gnomAD: https://gnomad.broadinstitute.org/variant/chr12-6021960-C-T?dataset=gnomad_r4