Case#: Elayaperumal_2018_V-225 , M, 1 month (onset), origin in India

DiseaseAssertion: VWD type 3

FamilyInfo: consanguinity not reported, family history negative

ParentalGenotype: not reported

CasePresentingHPOs:

CaseHPOFreeText: bleeding score 16, VWF:Ag 0, FVIII:C 4.1%

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: not reported

GenotypingMethod: CSGE and Sanger sequencing of VWF gene only.

Gene: VWF

Variant: homozygous c.1117C>T (p.Arg373*)

HGVS: NM_000552.3:c.1117C>T

ClinVarID: 100175

CAID: CA228261

gnomAD: Popmax (0.00004448 ) in the south Asian population (4/30550 alleles). 0 homozygotes reported.

MultipleGeneVariants:

Case: 7, F, 4 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: 24

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1117C>T (p.Arg373*), Exon 10, Homozygous

Case: 8, F, 2 years, Indian

DiseaseAssertion: VWD type 3

FamilyInfo: Consanguinity: no, no family history of disease

ParentalGenotype: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: FVIII:C: (U/dl): 4.5, VWF:Ag (U/dl): <1, Bleeding Score: 11

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

CasePreviousTesting: n/a

Gene: VWF

Variant:

c.1117C>T (p.Arg373*), Exon 10, Homozygous

Case: 29, M, 16, Indian

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:

1117C→T (Arg373X), Exon 10, Homozygous

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