Case-Individual:

Case: 50-year old male of consanguinous parents

DiseaseAssertion: severe Type 1 Von Willebrand Disease, previously misclassified as Type 3

Family Info: Proband's parents and offspring had the same mutation, but at the heterozygous level; all asymptomatic

Parental Genotype: N/A

CasePresentingHPOs: HP:0000421, HP:0030140, HP:0006298, HP:0005261

Epistaxis, oral cavity bleeding, severe hemorrhagic complications after tooth extractions (HP is called Prolonged bleeding after dental extraction), hemarthrosis (joint bleeding)

CaseHPOFreeRext: Lifelong history of severe bleeding, frequent hematomas, bleeding from minor wounds (possibly HP:0030138, excessive bleeding from superficial cuts), impaired hemostatic picture, extremely high ISTH bleeding score (proband's was 30 whereas males usually range from 0-3)

CaseNOTHPOs: N/A

CaseNOTHPOFreeText: N/A

CasePreviousTesting: N/A

GenotypingMethod: Sequencing reactions were performed in an ABI3130 XL Genetic Analyzer; digital droplet polymerase chain reaction (ddPCR) assays were performed (in multiplex); in vitro expression also performed, then electrophoresis system used to run Western blot

Gene: VWD

HGVS: NM_000552.5:c.2269_2270del

Variant: Gene null homozygous c.2269_2270del mutation

ClinVarID: 100207

CAID: CA228313

gnomAD: MAF of 0.000002542 (3 of 1180022 alleles) in the European non-Finnish population

Case: Croatian adult patient

DiseaseAssertion: VWD1

FamilyInfo: Not specified

ParentalGenotype(s): Not specified

CasePresentingHPOs: HP:0001892, HP:0011890, HP:0000132, HP:0002239, HP:0000790, HP:0001342

CaseHPOFreeText: Reduced VWF:GPIbM of 41.3%. Normal VWF:Ag of 67.8%, FVIII:C of 72% and VWF:CBA of 50.5%. Normal multimer distribution.

CaseNOTHPOs: Not specified

CaseNOTHPOFreeText: Normal multimer size distribution (tested in Agarose gel).

CasePreviousTesting: Not reported

GenotypingMethod: Illumina NGS, custom designed panel covering all 52 exons as well as intronic flanking regions and promoter region of VWF gene.

PreviouslyPublished: PMID: 34351388

Gene: VWF

Variant: c.2269_2270delCT

HGVS: NM_000552.4:c.2269_2270delCT (p.Leu757ValfsTer22)

ClinVarID: 100207

CAID: CA228313

**gnomAD: ** 0.000008794 in European (non-Finnish), 0.0003115 in XX and 0.0001629 in XY

https://gnomad.broadinstitute.org/variant/12-6155899-CAG-C?dataset=gnomad_r2_1