Case: Patient from family A, a 23-year-old female consanguineous Chinese patient

DiseaseAssertion: Type 3 von Willebrand disease

FamilyInfo: Patient's parents were cousins, both heterozygous carriers, who had also had a son that died at 1 year old from heavy nose bleeding; no other details given

ParentalGenotype(s): Heterozygous carriers, no details given as far as specific genotypes

CasePresentingHPOs: HP:0000132

Menorrhagia

CaseHPOFreeRext:"When she was 2 years old, scalp hematoma was observed." and severely decreased FVIII:C, VWF:Ag (FVIII:C: 1.3%, VWF:Ag: 3.6%, VWF:RCo: <1.0%)

CaseNOTHPOs: N/A

CaseNOTHPOFreeText: "No mutation was found in the F8 or F9 gene"

CasePreviousTesting: N/A

GenotypingMethod: NGS was performed targeting all exons and intronic flanking regions of the F8 (OMIM: * 300841, NM_000132.3), F9 (OMIM: * 300746, NM_000133.3), and VWF (OMIM: * 613160, NM_000552.4) genes; Some exons of VWF gene could not be discriminated from its highly homologous pseudogene, and these exons were sequenced by Sanger sequencing

Gene: VWF

Variant: Homozygous VWF c.4696C>T (p.Arg1566Ter) nonsense mutation

HGVS: NM_000552.5:c.4696C>T

ClinVarID: 100382

CAID: CA228639

gnomAD: MAF of 0.00001333 (1/74998 alleles) in the African/African American population

Case#: Patient A, Female, Age 23, Chinese

Disease Assertion: VWD3

FamilyInfo: Family pedigree in figure 1(a). Consanguineous marriage between parents. Parents had a boy who died (1 year old) due to heavy nose bleeds. Parents were heterozygous carriers for the variant.

Parental Genotype: Both parents were heterozygous

CasePresentingHPOs: HP:0000132, HP:0003645, HP:0008151

(Menorrhagia, Prolonged partial thromboplastin time, Prolonged prothrombin time)

CaseHPOFreeText: Scalp hematoma, FVIII:C: 1.3%, VWF:Ag: 3.6%, VWF:RCo: <1.0%, PT: 15.9 s, APTT: 62.7 s

CaseNotHPOs: N/A

CaseNotHPOFreeText: TT: 14.9 s

Protein Expression: N/A

CasePreviousTesting: NGS targeting all exons and covered F8,F9, and VWF genes; and Sanger Sequencing

Gene: VWF

Variant: NM_000552.4(VWF):c.4696C>T (p.Arg1566Ter)

ClinVar:100382 ClinVarID

CAID: CA228639

CAID

gnomAD: MAF of 0.00001762 (2/113480 alleles) in the European (Non- Finnish) population.

gnomAD