Case: 64, M, 2 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: no family history of disease, Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 5.2, VWF:Ag (U/dl): <1, Bleeding Score: 6

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3835G>A (p.Val1279Ile), Exon 28

c.3931C>T (p.Gln1311*), Exon 28

Homozygous

Case: 67, M, 13 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: family history of disease, Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): 2.6, Bleeding Score: 7

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3686T>G (p.Val1229Gly), Exon 28

c.3692A>C (p.Asn1231Thr), Exon 28

c.3931C>T (p.Gln1311*), Exon 28

Homozygous

Case: 30, M, 1.1 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: yes, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): <1, VWF:Ag (U/dl): <1, Bleeding Score: 4

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3931C>T (p.Gln1311*), Exon 28, Homozygous

Case: 63, M, 14 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: no family history of disease, Consanguinity: yes

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 7.5, VWF:Ag (U/dl): <1, Bleeding Score: 16

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3931C>T (p.Gln1311*), Exon 28

c.4027A>G (p.Ile1343Val), Exon 28

c.4079T>C (p.Val1360Ala), Exon 28

Homozygous

Case: 80, F, 12 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no, family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 3.2, VWF:Ag (U/dl): <1, Bleeding Score: 2

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3931C>T (p.Gln1311*), Exon 28, Homozygous

Case: 66, F, 5 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: no family history of disease, Consanguinity: no

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 1.4, VWF:Ag (U/dl): 2.3, Bleeding Score: 6

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3862C>G (p.Leu1288Val), Exon 28

c.3931C>T (p.Gln1311*), Exon 28

c.3951C>T (p.Ala1317Ala), Exon 28

c.4027A>G (p.Ile1343Val), Exon 28

Heterozygous

Case: 65, M, 10 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: no family history of disease, Consanguinity: no

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 2.1, VWF:Ag (U/dl): 1.4, Bleeding Score: 5

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.3789G>A (p.Ser1263Ser), Exon 28

c.3797C>T (p.Pro1266Leu), Exon 28

c.3835G>A (p.Val1279Ile), Exon 28

c.3931C>T (p.Gln1311*), Exon 28

c.3951C>T (p.Ala1317Ala), Exon 28

Homozygous

Case#: Elayaperumal_2018_V-282, F, 2 y.o. (onset), origin in India

DiseaseAssertion: VWD type 3

FamilyInfo: reportedly not-consanguineous. No family history of bleeding.

ParentalGenotype: not reported

CasePresentingHPOs:

CaseHPOFreeText: bleeding score of 17, VWF:Ag of 0, FVIII:C 4.3%

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: not reported

GenotypingMethod: CSGE and Sanger sequencing of VWF gene only.

Gene: VWF

Variant: heterozygous c.2683C>T (Gln895), c.3835G>A (p.Val1279Ile), c.3931C>T (p.Gln1311)

HGVS: NM_000552.3:c.2683C>T, NM_000552.3:c.3835G>A, NM_000552.3:c.3931C>T

ClinVarID: -,100288,100307

CAID: -, CA228459, CA228496

gnomAD: 1: not found 2: MAF of 0.002604 (27/10370 allele, Ashkenazi Jewish) https://gnomad.broadinstitute.org/variant/12-6128749-C-T?dataset=gnomad_r2_1 3:

MultipleGeneVariants:

Case: 20, F, 20, Iranian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: Yes

ParentalGenotype: n/a

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:

3931C→T (Gln1311X), Exon 28, Homozygous

3951C→T (Ala1317Ala)

Note: Mutation Gln1311X is likely due to a gene conversion; both mutations match the pseudogene sequence

Case#: 32010, Age 21, Male, Blood Type not determined (Table S3)

Disease Assertion: VWD 1

FamilyInfo: The patient is one of two members of Family#3210. The second member is a carrier of the variant c.3931C>T.

Parental Genotype: Not listed

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding Score 12, VWF:Ag:7.2, VWF:RCo: 5.7, FVIII:C: 21, VWF:CB: 6.8

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.3931C>T (p.Gln1311Ter) and NM_000552.4:c.55G>A (p.Gly19Arg)

ClinVar: 100307 and 100432 ClinVar1 ClinVar

CAID: CA228496 and CA228729 CAID1 CAID2

gnomAD: MAF of 0.0003921 (12/ 30604 alleles) in the South Asian population (CA228496). gnomAD

MAF of 0.0008819 (27/ 30616 alleles) in the South Asian population.

gnomAD

Case: T090, M, 2

DiseaseAssertion: VWD type 3

FamilyInfo: inherited heterozygous gene conversion from the father

CasePresentingHPOs: n/a

CaseHPOFreeText: Bleeding Score: 8 (Kruskal–Wallis followed by Mann–Whitney U post-hoc testing Post-hoc testing ), VWF:Ag (IU/ml): 0.01, VWF:RCo (IU/ml): 0.04, FVIII:C (IU/ml): 0.01

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1117C>T (p.Arg373*)

Gene Conversion (

c.3931C>T (p.Gln1311*)

c.4027A>G (p.Ile1343Val)

c.4079T>C (p.Val1360Ala)

c.4105T>A (p.Phe1369Ile)

)

Exon 10/28

Compound heterozygous

Note: ELISA-based assay for detecting alloantibodies, genomic analysis via sequencing of leukocytes for the VWF gene including exons 1-52 and about 1.5 km of VWF promoter, PCR amplification for variant confirmation, SALSA-MLPAVWF assay evaluation for partial/total gene deletions when sequencing did not reveal pathogenic explanation