Case: Female, Caucasian, 11 years at diagnosis

DiseaseAssertion: VWD1

FamilyInfo: Non-consanguineous family, parents carry no bleeding history but have risk factors (prolonged closure time and modestly decreased VWF:Ag level)

ParentalGenotype(s): Mother has c.7464C>T, Father carries no mutation.

CasePresentingHPOs: HP:0000421, HP:0000978, HP:0001934, HP:0030140, HP:0004846, HP:0006298

CaseHPOFreeText: Cumulative bleeding score of 17, Reduced VWF:Ag of 9IU/dL, VWF:GPIb of 6 I/dL, and factor VIII coagulant activity of 35 IU/dL, prolonged PFA closure time of >300 and reduced concentration of all multimers.

CaseNOTHPOs: None reported

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

CasePreviousTesting: NA

GenotypingMethod: Direct sequencing of genomic DNA exons 1 to 52, exon/intron boundaries, 5' and 3' UTR, promoter region, and whole intron 44 of VWF. RT-PCR followed by sequencing of cDNA to detect splicing defect due to c.7464C>T.

PreviouslyPublished: PMID:22871923

Gene: VWF

Variant: c.7464C>T

HGVS: NM_000552.5:c.7464C>T (p.Gly2488=)

ClinVarID: 619755

CAID: CA232284628

gnomAD: 0.000008799 MAF in European (non-Finnish) and 0.000008664 MAF in XX. https://gnomad.broadinstitute.org/variant/12-6080849-G-A

Case1: Female patient, 37-year-old, At age 25(pregnant) an F8 mutation was identified, Family History of Severe HA

DiseaseAssertion: Mild hemophilia A due to a family mutation and de novo mutation

FamilyInfo: Family also has the large deletion of exon 1 to 22 of the F8 gene, Son (age 10) has mild Hemophilia A

ParentalTesting: Father tested negative for any F8 mutations, Mother is an asymptomatic carrier of the familial large deletion

CasePresentingHPOs: HP:0000978 (Bruising Susceptibility), HP:0000132 (Menorrhagia)

CaseHPOFreeText: FVIII:C 7%, compounded heterozygous for the large gene deletion and c.1569G>T mild mutation

CasePreviousTesting: Molecular analysis, Sequenced the whole coding region of the F8 gene

Gene: F8

Variant: 1. F8, EX1-22DEL 2. NM_000132.3:c.1569G>T (p.Leu523=)

ClinVar: 1. 10122 https://www.ncbi.nlm.nih.gov/clinvar/variation/10122/

1. 439678 https://www.ncbi.nlm.nih.gov/clinvar/variation/439678/

gnomAD: 1. Not reported (F8, EX1-22DEL)

1. MAF for Leu523= in Latino population 0.00007293 <br /> https://gnomad.broadinstitute.org/variant/X-154185415-C-A?dataset=gnomad_r2_1