Case#: P3 (female)

DiseaseAssertion: Carrier

FamilyInfo: N/A

ParentalTesting: Father was tested; has mild HA

CasePresentingHPOs: HP:0003125, HP:0001928

CaseHPOFreeText: Low FVIII levels (significant decrease in FVIII:C (48.4% ± 6.1, P < 0.01) and FVIII:Ag (36.6% ± 2.7, P < 0.01)), abnormal blood coagulation

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

CasePreviousTesting: Molecular Analysis included a southern blot assay, PCR, dHPLC and a multiplex ligation-dependent probe amplification analysis. Plasmid mutagenesis, plasmid transfection and in silico analysis were also performed.

Gene: F8

Variant: NM_000132.4:c.1562C>T

CAID: CA414912242

gnomAD: Absent/Not Reported

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