Activation of the Fibrinogen Binding Site on Platelets Isolated From a Patient With the Strasbourg I Variant of Glanzmann's Thrombasthenia
PMID: 8049427
Gene: ITGB3
HGNC: 6156
2,172 Matching Annotations
- Oct 2026
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watermark.silverchair.com watermark.silverchair.com1108.pdf1
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ashpublications.org ashpublications.org
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Major mutations in calf-1 and calf-2 domains of glycoprotein IIb in patients with Glanzmann thrombasthenia enable GPIIb/IIIa complex formation, but impair its transport from the endoplasmic reticulum to the Golgi apparatus
PMID: 12609844
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions 2 major mutations in the calf-1 and calf-2 domains of ITGA2B. There are no specific Glanzmann thromasthenia patients mentioned that harbor these specific variants; therefore, there is insufficient evidence
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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R to Q amino acid substitution in the GFFKR sequence of the cytoplasmic domain of the integrin IIb subunit in a patient with a Glanzmann's thrombasthenia-like syndrome.
PMID: 9834222
Gene: ITGA2B
HGNC: 6138
NOTE: Curated on Pubmed abstract because blood journal is not saving annotations correctly
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www.ahajournals.org www.ahajournals.org
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Two Types of Procoagulant Platelets Are Formed Upon Physiological Activation and Are Controlled by Integrin αIIbβ3
PMID: 22837472
Genes: ITGA2B and ITGB3
HGNC: 6138 and 6156
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Local file Local file
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Clinical Case Report
PMID: 14606769
Gene: ITGB3
HGNC: 6156
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Glanzmann Thrombasthenia in Children From Argentina
PMID: 8556365
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions 10 GT patients; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
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Local file Local file
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PLATELET TRANSFUSION IN A PATIENT AFFECTED BY GLANZMANN'STHROMBASTHENIA WITH ANTIBODIES AGAINST GPIIb-IIIa
PMID: 9107089
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
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www.tandfonline.com www.tandfonline.com
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Diagnosis of platelet function disorders: A standardized, rational, and modular flow cytometric approach
PMID: 29227167
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article is about developing a standardized and modular flow cytometric approach, that contributes to clarify impaired platelet function in a rational step by step manner. There is no mention of variants in probands for ITGA2B or ITGB3
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ashpublications.org ashpublications.org
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Identification of a region in glycoprotein IIIa involved in subunit association with glycoprotein IIb: further lessons from Iraqi-Jewish Glanzmann thrombasthenia
PMID: 11719373
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B/ITGB3; however, no probands discussed in this article
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ashpublications.org ashpublications.org
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Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1
PMID: 12791669
Gene: ITGB3
HGNC: 6156
InsufficientEvidence: This article mentions a variant in ITGB3; however, there is no mention of a proband with this variant
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Glanzmann's Thrombastenia: The Role of Tranexamic Acid in Oral Surgery
PMID: 30254767
Gene: ITGA2B and/or ITGB3 (Proband diagnosed with Gt therefore these genes may be involved here)
HGNC: 6138 and 6156
InsufficientEvidence: Proband with Glanzmann Thrombasthenia described here however no mention of variants therefore insufficient evidence
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reader.elsevier.com reader.elsevier.com
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BlockingPlateletAggregationInhibitsThromboxaneA2FormationbyLowDoseAgonistsButDoesNotInhibitPhosphotylationandActivationofCytosolicPhospholipaseA2.
PMID: 9361365
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156, respectively
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3. In this study, they made use of Ro 44-9883 as a potent non-peptide GPIIb/IIIa antagonist to address the relationship of platelet aggregation to PLA2 activation, TxA2 formation, and granule secretion.
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www.jbc.org www.jbc.org
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Mechanistic Insights from a Refined Three-dimensionalModel of IntegrinIIb3*
PMID: 15056669
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions Glanzmann thrombasthenia variants; however, no patients with GT are mentioned with these variants therefore we have insufficient evidence
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ashpublications.org ashpublications.org
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Fibrin-Dependent Platelet Procoagulant Activity Requires GPIb Receptors and von Willebrand Factor
PMID: 9885217
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article references a GT patient, which was reported as a case report in another article; however, no specific case reports are mentioned in this article
PreviouslyPublished: PMID: 2014236
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www.jbc.org www.jbc.org
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Critical Residues of IntegrinaIIb Subunit for Binding ofaIIbb3(Glycoprotein IIb-IIIa) to Fibrinogen and Ligand-mimeticAntibodies (PAC-1, OP-G2, and LJ-CP3)*
PMID: 8702512
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B and/or ITGB3; however, there are no Glanzmann thrombasthenia case reports mentioned in this article therefore we have insufficient evidence
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instructure-uploads.s3.amazonaws.com instructure-uploads.s3.amazonaws.com
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Three Novel Integrinb3 Subunit Missense Mutations(H280P, C560F, and G579S) in Thrombasthenia, IncludingOne (H280P) Prevalent in Japanese Patients
PMID: 9790984
Gene: ITGB3
HGNC: 6156
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Triple heterozygosity in the integrin αIIb subunit in a patient with Glanzmann's thrombasthenia
PMID: 15099289
Gene: ITGA2B
HGNC: 6138
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Local file Local file
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Coronary Artery Bypass Grafting in aPatient with Glanzmann’sThrombasthenia
PMID: 16309410
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with GT'; however, no variants in ITGA2B and/or ITGB3 are mentioned therefore we have insufficient evidence
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Thalidomide for the Treatment of Gastrointestinal Bleeding Due to Angiodysplasia in a Patient with Glanzmann’s Thrombasthenia
PMID: 28670433
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article describes a proband with Glanzmann thrombasthenia; however, there is no mention of variants in ITGA2B and ITGB3 in this proband.
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Glanzmann's Thrombasthenia Diagnosed following Knee Arthroscopy
PMID: 26000186
Gene: Patient could have variation in ITGA2B or ITGB3, article does not specify; however, patient has GT so it is implied one of the two genes is involved
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband who was diagnosed with Glanzmann thrombasthenia; however, there is no mention of variants in ITGA2B or ITGB3 in this patient; therefore, we have insufficient evidence
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www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
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Binding of plasma factor XIII to thrombin-receptor activated human platelets
PMID: 19572072
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients with variants in ITGA2B and/or ITGB3
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Local file Local file
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aIIbG236E causes Glanzmann thrombasthenia by impairingassociation withb3
PMID: 18791937
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
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ashpublications.org ashpublications.org
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A dinucleotide deletion in exon 4 of the PlA2 allelic form of glycoprotein IIIa: implications for the correlation of serologic versus genotypic analysis of human platelet alloantigens
PMID: 8916947
Gene: ITGB3
HGNC: 6156
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Total Extraction as a Treatment for Anaemia in a Patient of Glanzmann’s Thrombasthenia with Chronic Gingival Bleed: Case Report
PMID: 26894187
Gene: ITGA2B and/or ITGB3 (Article does not explicitly state these genes; however, patient has Glanzmann thrombasthenia so these two genes are implied)
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an 18 year old male patient with Glanzmann thromasthenia; however, there are no variants in ITGA2B or ITGB3 that are mentioned here
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pdfs.semanticscholar.org pdfs.semanticscholar.org
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Glanzmann’s Thrombasthenia Associated With Deletion-Insertion and Alternative Splicing in the Glycoprotein IIb Gene
PMID: 7529063
Gene: ITGA2B
HGNC: 6138
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Local file Local file
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A systematic review of the management and outcomes ofpregnancy in Glanzmann thrombasthenia
PMID: 21457404
Genes: ITGA2B and ITGB3
HGNC: 6138 and 6156
Insufficient Evidence: This article reports the results of a systematic review of management and outcome data contained within all published descriptions of pregnancy in GT. Probands with GT are mentioned; however, no variants are mentioned.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia.
PMID: 8781422
Gene: ITGB3
HGNC: 6156
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Local file Local fileRCH521
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INHERITEDDEFECTS OFPLATELETFUNCTION
PMID: 11844132
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B and ITGB3; however, there are no specific Glanzmann thrombasthenia patients with the mentioned variants; therefore, there is insufficient evidence
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watermark.silverchair.com watermark.silverchair.com
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Carrier Detection in Glanzmann ThrombastheniaComparison of Flow Cytometry and Western Blot With Respect to DNA Mutation
PMID: 18550477
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions probands with GT; however, the probands are clumped together, and variants are not specifically tied to probands
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Local file Local file
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Concomitant occurrence of mucopolysaccharidosis IIIB and Glanzmann's thrombasthenia. Further
PMID: 1606713
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient and family members of the patient; however, there is no mention of variants in ITGA2B and/or ITGB3; therefore, there is insufficient evidence
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ashpublications.org ashpublications.org
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Two novel mutations in the αIIb calcium-binding domains identify hydrophobic regions essential for αIIbβ3 biogenesis
PMID: 12424194
Gene: ITGA2B
HGNC: 6138
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Local file Local file2002; 041
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Glanzmann’s thrombasthenia: modulation of clinical phenotype by α2C807Tgene polymorphism
PMID: 14687991
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
PreviouslyPublished: All probands in this article have been previously published in PMID: 12083483 therefore this paper is not being curated
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Homozygous Cys542→Arg substitution in GPIIIa in a Swiss patient with type I Glanzmann's thrombasthenia
PMID: 10233432
Gene: ITGB3
HGNC: 6156
Note: Other GT variants are mentioned at the end of the article; however, those have been mentioned in other papers-- and probands with those mentioned variants are not apart of this paper
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Glanzmann's thrombasthenia due to a point mutation within intron 10 results in aberrant splicing of the β3 gene
PMID: 14629479
Gene: ITGB3
HGNC: 6156
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www.ahajournals.org www.ahajournals.org
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Platelet Integrin αIIbβ3 (GPIIb-IIIa) Is Not Implicated in the Binding of LDL to Intact Resting Platelets
PMID: 9012651
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Periodontal considerations for Glanzmann's thrombasthenic patient
PMID: 20142940
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of a 9 year old GT patient who presented with gum bleeding; however, no specific variants in ITGA2B and/or ITGB3 are presented in this patient; therefore we have insufficient evidnece
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Acquired Glanzmann's thrombasthenia associated with acute lymphoblastic leukemia.
PMID: 16217260
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with GT; however, no variants in ITGA2B and/or ITGB3 are mentioned therefore we have insufficient evidence
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www.sciencedirect.com www.sciencedirect.com
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Correction of a large animal model of type I Glanzmann's thrombasthenia by nonmyeloablative bone marrow transplantation
PMID: 14662345
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article mentions dogs with GT; however, the article states, "These animals have a 14-base insertion in exon 13 of glycoprotein IIb gene" which is a variant in ITGA2B. This variant may only be specific to dogs; however, just wanted to make note of this gene alteration.
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Local file Local file
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Menorrhagia due to abnormalities of the platelet function: Evaluation of two young patients
PMID: 17250517
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions two GT case reports of girls with menorrhagia; however, there was no mention of variants in ITGA2B and/or ITGB3; therefore there is insufficient evidence
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ashpublications.org ashpublications.org
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A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in the expression of a GPIIb-IIIa (αIIbβ3) integrin receptor locked in a high-affinity state and a Glanzmann thrombasthenia–like phenotype
PMID: 11588040
Gene: ITGB3
HGNC: 6156
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-
www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
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Rapid diagnosis of the French gypsy mutation in Glanzmann thrombasthenia using high- resolution melting analysis
PMID: 20886184
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article discusses the French Gypsy variant NM_000419.3:c.1544+1G>A (p.Val513Leufs*71) in ITGA2B and mentions a cohort of patients harboring this variant; however, there are no specific case level reports mentioned in this article therefore we have insufficient evidence
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Local file Local fileuntitled1
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Molecular defects inITGA2Band ITGB3 genes in patientswith Glanzmann thrombasthenia
PMID: 19691478
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
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Local file Local file
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A unique phenotype of acquired Glanzmann thrombastheniadue to non-function-blocking anti-aIIbb3 autoantibodies
PMID: 30388316
Gene: ITGA2B and/or ITGB3 (Proband presented with GT therefore these two genes may be involved)
HGNC: 6138 and 6156
InsufficientEvidence: Proband with Glanzmann thrombasthenia presented in this article; however, no variant information provided
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Local file Local file
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Expanding the Mutation Spectrum AffectingαIIbβ3Integrin in Glanzmann Thrombasthenia: Screening of theITGA2BandITGB3Genes in a Large International Cohor
PMID: 25728920
Genes: ITGA2B and ITGB3
HGNC: 6138 and 6156
Note: In the annotations, case #'s don't always match up with the exact proband #, because not all probands had GT variants identified in them
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Type I Glanzmann Thrombasthenia: Most CommonSubtypes in North Indians
PMID: 14508803
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions GT patients however no variants in ITGA2B and/or ITGB3 are mentioned in these patients.
In this study the goal was to determine what the common subtype of GT was: The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects
PMID: 23300803
Genes: ITGA2B and ITGB3
HGNC: 6138 an d 6156
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Local file Local file
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Identifying human platelet glycoproteins IIb and IIIa by capillary electrophoresis
PMID: 9694297
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Epistaxis as a Common Presenting Symptom of Glanzmann's Thrombasthenia, a Rare Qualitative Platelet Disorder: Illustrative Case Examples
PMID: 28299211
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions cases of patients with Glanzmann thrombasthenia and their phenotypes; however, no mention of variants in ITGB3 or ITGA2B
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jcs.biologists.org jcs.biologists.org
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Talin distribution and phosphorylation in thrombin-activated platelets
PMID: 8126100
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT probands or variants in ITGA2B and ITGB3. In this study, researchers have examined the talin phosphorylation and proteolytic cleavage as possible mechanisms by which talin's subcellular distribution could be regulated in platelets.
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Local file Local file
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A New Case of Acquired Glanzmann’sThrombasthenia: Diagnostic Value ofFlow Cytometry
PMID: 18200593
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a 27 year old proband with Glanzmann thrombasthenia; however, no variants in ITGA2B and/or ITGB3 were mentioned in this proband therefore we have insufficient evidence
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academic.oup.com academic.oup.com
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Novel GDAP2 pathogenic variants cause autosomal recessive spinocerebellar ataxia-27 (SCAR27) in a Chinese family
PMID: 32437512
Gene: GDAP2
HGNCID: HGNC:18010
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www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
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071–2003
Case#: 071-2003
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.4825dupA
LegacyVariant:
ClinVar: No
CAID: CA255152
gnomAD:
-
001–1026
Case#: 001-1026,...
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
047–1004
Case#: 047-1004
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
080–2002
Case#: 080-2002
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1649G>A
LegacyVariant:
ClinVar: No
CAID: CA255115
gnomAD:
-
048–1002
Case#: 048-1002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
038–2002
Case#: 038-2002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5687_5690delCT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
016–2001
Case#: 016-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.901C>T
LegacyVariant:
ClinVar: No
CAID: CA414917990
gnomAD:
-
003–2005
Case#: 003-2005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5275delG
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
071–2007
Case#: 071-2007
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1208A>C
LegacyVariant:
ClinVar: No
CAID: CA414916134
gnomAD:
-
060–2009
Case#: 060-2009
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1834C>T
LegacyVariant:
ClinVar: No
CAID: CA255129
gnomAD:
-
016–2003
Case#: 016-2003
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.2129G>A
LegacyVariant:
ClinVar: No
CAID: CA414904142
gnomAD:
-
020–1011
Case#: 020-1011
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
004–2017
Case#: 004-2017
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
-
091–2004
Case#: 091-2004
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5281T>C
LegacyVariant:
ClinVar: No
CAID: CA414911024
gnomAD:
-
038–2025
Case#: 038-2025
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.514T>G
LegacyVariant:
ClinVar: No
CAID: CA414919550
gnomAD:
-
016–2005
Case#: 016-2005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.3531_3533delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
004–2008
Case#: 004-2008
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.4379dupA
LegacyVariant:
ClinVar: No
CAID: CA645292749
gnomAD:
-
035–2021
Case#: 035-2021
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5954G>A
LegacyVariant:
ClinVar: No
CAID: CA414905715
gnomAD:
-
035–1005
Case#: 035-1005
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1271þ1G>C
LegacyVariant:
ClinVar: No
CAID: CA414915615
gnomAD:
-
038–2011
Case#: 038-2011
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5252A>G
LegacyVariant:
ClinVar: No
CAID: CA414911251
gnomAD:
-
020–2057
Case#: 020-2057
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
-
035–2019
Case#: 035-2019
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.923C>T
LegacyVariant:
ClinVar: No
CAID: CA255082
gnomAD:
-
035–2001
Case#: 035-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1963_1964insT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
071–2027
Case#: 071-2027
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.4184_4186delGGAinsCCTC
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
020–1016
Case#: 020-1016
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
015–2006
Case#: 015-2006
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.343G>T
LegacyVariant:
ClinVar: No
CAID: CA414919965
gnomAD:
-
060–2001
Case#: 060-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
-
066–2003
Case#: 066-2003
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1649G>A
LegacyVariant:
ClinVar: No
CAID: CA255115
gnomAD:
-
010–1001
Case#: 010-1001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.6742T>A
LegacyVariant:
ClinVar: No
CAID: CA414904758
gnomAD:
-
002–2002
Case#: 002-2002
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.2092T>C
LegacyVariant:
ClinVar: No
CAID: CA414908999
gnomAD:
-
038–2023
Case#: 038-2023
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.322_332þ8delGCTTCTGAGGGtgagtaaa
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
002–2006
Case#: 002-2006
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.4379delA
LegacyVariant:
ClinVar: No
CAID: CA255151
gnomAD:
-
001–2040
Case#: 001-2040
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5630G>A
LegacyVariant:
ClinVar: No
CAID: CA414908131
gnomAD:
-
003–2001
Case#: 003-2001
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.493C>T
LegacyVariant:
ClinVar: No
CAID: CA255065
gnomAD:
Tags
- DiseaseEntity:FactorVIIIDeficiency
- CAID:CA414904758
- CAID:CA255065
- CAID:CA255152
- CAID:CA255151
- ParentalTest:Unknown
- CAID:CA414916134
- Mutation:Large
- DiseaseSeverity:SevereHemophiliaA
- ClinGen Coag Fac Def VCEP
- FIXtesting:Partial
- UnregisteredVariant
- CAID:CA414904142
- Inhibitor:NotReported
- CAID:CA414919965
- CAID:CA414915615
- Gene:F8
- HGNC:3546
- AssayDiscrepancy:NotReported
- Inhibitor:Present
- CAID:CA414908999
- PreviousTesting:None
- inferred_gene_source:hgnc_tag
- Mutation:Missense
- InheritancePattern:NoInheritanceAssertion
- Mutation:Intronic
- CAID:CA414911024
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
- CAID:CA414917990
- CAID:CA414908131
- CAID:CA255129
- CAID:CA414919550
- DiseaseSeverity:ModerateHemophiliaA
- inferred_gene_hgnc:3546
- CAID:CA255115
- CAID:CA414911251
- CAID:CA645292749
- Mutation:Splice
- CaseInfo
- Mutation:InframeDelins
- SupplementalData
- DiseaseSeverity:MildHemophiliaA
- CAID:CA414905715
- Inhibitor:Absent
- CAID:CA255082
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Single synonymous mutation in Factor IX alters protein properties and underlies hemophilia B
PMID: 28007939
Gene: F9
HGNCID: 3551
-
-
www-thieme-connect-com.libproxy.lib.unc.edu www-thieme-connect-com.libproxy.lib.unc.edu
-
c.681G>T
Case#: 6
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1% (Severe Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, Possibility that sample was blinded for NGS and then validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.681G>T (p.Trp227Cys)
ClinVar: NA
CAID: CA414919155
gnomAD: Not reported
-
c.1288T>C
Case1: 9
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 17% (Mild Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.1288T>C (p.Tyr430His)
ClinVar: NA
CAID: CA337336221
gnomAD: Not reported
-
c.6113A>G
Case#: 28
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 5/3% (Moderate Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.6113A>G (p.Asn2038Ser)
ClinVar: 10305 https://www.ncbi.nlm.nih.gov/clinvar/variation/10305/
CAID: CA255198
gnomAD: Not reported
-
IVS22
Case#: 30
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1%, Severe Phenotype, Inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, possibility that sample was blinded for NGS and validated by comparing results with Sanger Sequencing
Gene: F8
Variant: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/#id_second
gnomAD: Not reported
-
c.226G>C
Case#: 41
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.226G>C (p.Glu76Gln)
ClinVar: NA
CAID: CA414436160
gnomAD: Not reported
-
c.1648C>T
Case#: 13
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 25/21% (Mild Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.1648C>T (p.Arg550Cys)
ClinVar: 10223 https://www.ncbi.nlm.nih.gov/clinvar/variation/10223/
CAID: CA255113
gnomAD: Not reported
-
c.5999–740T>C
Case#: 26
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 33%, Mild Phenotype, No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.5999-740T>C
ClinVar: NA
CAID: CA1139532039
gnomAD: Not reported
-
c.1052G>A
Case#: 39
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.1052G>A (p.Gly351Asp)
ClinVar: NA
CAID: CA414445595
gnomAD: Not reported
-
c.6046C>T
Case#: 27
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 4% (Moderate Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.6046C>T (p.Arg2016Trp)
ClinVar: 10304 https://www.ncbi.nlm.nih.gov/clinvar/variation/10304/
CAID: CA255197
gnomAD: Not reported
-
c.6750A>C
Case#: 35
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 24/32/19/17/35%, Mild Phenotype, No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.6750A>C (p.Gln2250His)
ClinVar: NA
CAID: CA414904711
gnomAD: Not reported
-
c.5936G>A
Case#: 25
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 21/17%, Mild Phenotype, No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.5936G>A (p.Gly1979Glu)
ClinVar: NA
CAID: CA414905839
gnomAD: Not reported
-
c.157G>A
Case#: 40
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C <1% (Severe Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.157G>A (p.Glu53Lys)
ClinVar: NA
CAID: CA414435726
gnomAD: Not reported
-
c.1025C>T
Case#: 48
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 3% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3(F9):c.1025C>T (p.Thr342Met)
ClinVar: 10607 https://www.ncbi.nlm.nih.gov/clinvar/variation/10607/
CAID: CA255381
gnomAD: Not reported
-
c.6506G>A
Case#: 31
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 17/25%, Mild Phenotype, inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.6506G>A (p.Arg2169His)
ClinVar: 10315 https://www.ncbi.nlm.nih.gov/clinvar/variation/10315/
CAID: CA255208
gnomAD: Not reported
-
c.1010–842G>A
Case#: 7
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 34/30/35% (Mild Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.1010-842G>A
ClinVar: NA
CAID: CA337336857
gnomAD: MAF in Ashkenazi Jewish population 0.01105<br>https://gnomad.broadinstitute.org/variant/X-154195804-C-T
Tags
- DiseaseEntity:FactorVIIIDeficiency
- ClinVarID:10304
- ParentalTest:Unknown
- CAID:CA414904711
- ClinGen Coag Fac Def VCEP
- FIXtesting:Partial
- CAID:CA255208
- CAID:CA337336221
- Gene:F8
- HGNC:3546
- inferred_gene_hgnc:3551
- ClinVarID:10315
- CAID:CA255381
- CAID:CA255198
- CAID:CA414919155
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- InheritancePattern:NoInheritanceAssertion
- Mutation:Intronic
- CAID:CA414436160
- ClinVarID:10223
- CAID:CA414905839
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
- CAID:CA414445595
- ClinVarID:10305
- CAID:CA255113
- CAID:CA1139532039
- Gene:F9
- inferred_gene_hgnc:3546
- HGNC:3551
- CAID:CA414435726
- ClinVarID:10607
- CaseInfo
- DiseaseEntity:FactorIXDeficiency
- CAID:CA255197
- ClinVarID:10150
Annotators
URL
-
-
onlinelibrary.wiley.com onlinelibrary.wiley.com
-
52
Case#: 52, male, 13 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1809C>G
LegacyVariant:
ClinVar: No
CAID: CA414910951
gnomAD:
-
151
Case#: 151, male, 17 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2621delT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
127
Case#: 127, male, 17 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2945dupA
LegacyVariant:
ClinVar: No
CAID: CA255142
gnomAD:
-
6
Case#: 6, male, 22 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1063C>T
LegacyVariant:
ClinVar: 10139
CAID: CA255031
gnomAD:
-
41
Case#: 41, male, 20 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.881C>T
LegacyVariant:
ClinVar: 10190
CAID: CA255077
gnomAD:
-
111
Case#: 111, male, 31 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.144-2A>G
LegacyVariant:
ClinVar: No
CAID: CA414920419
gnomAD:
-
39
Case#: 39, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.677G>A
LegacyVariant:
ClinVar: No
CAID: CA414919166
gnomAD:
-
107
Case#: 107, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 9.3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6814A>C
LegacyVariant:
ClinVar: No
CAID: CA414903910
gnomAD:
-
174
Case#: 174, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons1_26
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
93
Case#: 93, male, 45 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 18%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6444T>A
LegacyVariant:
ClinVar: No
CAID: CA414907970
gnomAD:
-
165
Case#: 165, male, 28 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.4339delG
LegacyVariant:
ClinVar: No
CAID: CA873341376
gnomAD:
-
122
Case#: 122, male, 33 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6115+1G>C
LegacyVariant:
ClinVar: No
CAID: CA414904456
gnomAD:
-
170
Case#: 170, male, 42 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6876_6877delCT
LegacyVariant:
ClinVar: No
CAID: CA873368227
gnomAD:
-
100
Case#: 100, male, 15 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6551A>C
LegacyVariant:
ClinVar: No
CAID: CA414907026
gnomAD:
-
29
Case#: 29, male, 21 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2.3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.337C>T
LegacyVariant:
ClinVar: No
CAID: CA414919977
gnomAD:
-
74
Case#: 74, male, 60 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 11%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5545T>A
LegacyVariant:
ClinVar: No
CAID: CA414908552
gnomAD:
-
87
Case#: 87, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3.9%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6406G>A
LegacyVariant:
ClinVar: No
CAID: CA414899430
gnomAD:
-
120
Case#: 120, male, 51 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5220-2A>G
LegacyVariant:
ClinVar: No
CAID: CA414911437
gnomAD:
-
60
Case#: 60, male, 19 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2029T>C
LegacyVariant:
ClinVar: 10244
CAID: CA255136
gnomAD:
-
104
Case#: 104, male, 13 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6683G>A
LegacyVariant:
ClinVar: 10098
CAID: CA255016
gnomAD:
-
138
Case#: 138, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.dup exons23_25
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
79
Case#: 79, male, 8 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5594A>G
LegacyVariant:
ClinVar: No
CAID: CA414908275
gnomAD:
-
2
Case#: 2, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.98G>A
LegacyVariant:
ClinVar: No
CAID: CA414920533
gnomAD:
-
182
Case#: 182, male, 25 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons15_26
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
12
Case#: 12, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1798G>T
LegacyVariant:
ClinVar: No
CAID: CA414911019
gnomAD:
-
9
Case#: 9, male, 19 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1285C>T
LegacyVariant:
ClinVar: No
CAID: CA414915370
gnomAD:
-
114
Case#: 114, male, 16 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.601+1G>C
LegacyVariant:
ClinVar: No
CAID: CA414919361
gnomAD:
-
5
Case#: 5, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.741G>A
LegacyVariant:
ClinVar: No
CAID: CA414919022
gnomAD:
-
64
Case#: 64, male, 6 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2158G>C
LegacyVariant:
ClinVar: No
CAID: CA414903786
gnomAD:
-
23
Case#: 23, male, 21 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6496C>T
LegacyVariant:
ClinVar: 10096
CAID: CA255013
gnomAD:
-
99
Case#: 99, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6544C>T
LegacyVariant:
ClinVar: 10321
CAID: CA255214
gnomAD:
-
92
Case#: 92, male, 61 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 4.2%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6440G>T
LegacyVariant:
ClinVar: No
CAID: CA414908004
gnomAD:
-
106
Case#: 106, male, 12 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6683G>A
LegacyVariant:
ClinVar: 10098
CAID: CA255016
gnomAD:
-
54
Case#: 54, male, 9 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 17%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1834C>T
LegacyVariant:
ClinVar: 10236
CAID: CA255129
gnomAD:
Tags
- DiseaseEntity:FactorVIIIDeficiency
- CAID:CA414919361
- Mutation:Frameshift
- Mutation:Nonsense
- Mutation:Large
- DiseaseSeverity:SevereHemophiliaA
- FIXtesting:Partial
- ClinGen Coag Fac Def VCEP
- UnregisteredVariant
- CAID:CA255214
- CAID:CA414907970
- ParentalConfirmation:Maternity
- ClinVarID:10139
- Gene:F8
- HGNC:3546
- ClinVarID:10098
- AssayDiscrepancy:NotReported
- CAID:CA414911019
- ClinVarID:10236
- Inhibitor:Present
- CAID:CA414919166
- CAID:CA414903786
- ToCheck
- CAID:CA414908552
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- CAID:CA414911437
- CAID:CA873341376
- CAID:CA414903910
- CAID:CA414915370
- CAID:CA873368227
- CAID:CA255031
- CAID:CA414919022
- CAID:CA255129
- CAID:CA414907026
- ClinVarID:10190
- CAID:CA255016
- Zygosity:Hemizygous
- CAID:CA255013
- CAID:CA414908004
- CAID:CA255077
- DiseaseSeverity:ModerateHemophiliaA
- CAID:CA255136
- inferred_gene_hgnc:3546
- CAID:CA414920419
- CAID:CA414908275
- ClinVarID:10096
- Mutation:Splice
- CaseInfo
- ClinVarID:10321
- CAID:CA255142
- CAID:CA414920533
- ClinVarID:10244
- CAID:CA414899430
- SupplementalData
- DiseaseSeverity:MildHemophiliaA
- CAID:CA414910951
- CAID:CA414904456
- Inhibitor:Absent
- CAID:CA414919977
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
S20
Case#: S20, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.2013_2015del
LegacyVariant:
ClinVar: No
CAID: CA873350278
gnomAD:
-
S29
Case#: S29, Iranian
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 30%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.2110C>T
LegacyVariant:
ClinVar: No
CAID: CA10568366
gnomAD:
-
S26
Case#: S26, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.3943delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S23
Case#: S23, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S5
Case#: S5, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.1010‐2A>G
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S15
Case#: S15, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Family history of HA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S12
Case#: S12, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Family history of HA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.del exons8_9
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S19
Case#: S19, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
Tags
- DiseaseEntity:FactorVIIIDeficiency
- Mutation:Frameshift
- ParentalTest:Unknown
- inferred_gene_hgnc:3546
- Mutation:Large
- DiseaseSeverity:SevereHemophiliaA
- ClinGen Coag Fac Def VCEP
- UnregisteredVariant
- CAID:CA10568366
- Mutation:Splice
- CaseInfo
- Gene:F8
- HGNC:3546
- AssayDiscrepancy:NotReported
- Inhibitor:Present
- ToCheck
- CAID:CA873350278
- Mutation:InframeDel
- inferred_gene_source:hgnc_tag
- Mutation:Missense
- Mutation:Intronic
- FVIIItesting:Partial
- Inhibitor:Absent
Annotators
URL
-
-
oce-ovid-com.libproxy.lib.unc.edu oce-ovid-com.libproxy.lib.unc.edu
-
Table 2
Case#: Cz24, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 1
Case#: Cz29, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/
CAID: NA
gnomAD: Not reported
-
Table 2
Case#: Cz1, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 2
Case#: Cz33, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 8%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 1
Case#: Cz12, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3(F8):c.5953C>T (p.Arg1985Ter)
ClinVar: 10300 https://www.ncbi.nlm.nih.gov/clinvar/variation/10300/
CAID: CA255191
gnomAD: Not reported
-
Table 1
Case#: Cz31, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1324T>C (p.Tyr442His)
ClinVar: NA
CAID: CA414915029
gnomAD: Not reported
-
Table 2
Case#: Cz11, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 2
Case#: Cz26, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 1.5%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 1
Case#: Cz37, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.4379dup (p.Asn1460LysfsTer2)
ClinVar: NA
CAID: CA645292749
gnomAD: MAF for p.Asn1460LysfsTer2 in the European (non-Finnish) population 0.00001245<br>https://gnomad.broadinstitute.org/variant/X-154157685-A-AT
Tags
- DiseaseEntity:FactorVIIIDeficiency
- Mutation:Frameshift
- CAID:CA873354114
- ParentalTest:Unknown
- inferred_gene_hgnc:3546
- Mutation:Nonsense
- ClinGen Coag Fac Def VCEP
- CAID:CA414915029
- InheritancePattern:Xlinked
- CAID:CA255191
- CaseInfo
- CAID:CA645292749
- Gene:F8
- HGNC:3546
- InheritancePattern:DeNovoAssertion
- ClinVarID:10300
- inferred_gene_source:hgnc_tag
- Mutation:Missense
- Mutation:Intronic
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
- ClinVarID:10150
- ClinVarID:811357
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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37-year old woman
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/
gnomAD: 1. Not reported (F8, EX1-22DEL)
- MAF for Leu523= in Latino population 0.00007293 <br /> https://gnomad.broadinstitute.org/variant/X-154185415-C-A?dataset=gnomad_r2_1
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a woman diagnosed as a HA carrier
Case2: Female patient, blood group O
DiseaseAssertion: Severe Hemophilia A from de novo mutation
FamilyInfo: Family history of severe Hemophilia A, Son diagnosed with severe HA, Sibling has intron 22 inversion on F8 gene
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeRext: aPTT ratio 1.16 (within normal range ratio), FVIII:C 48% (low-normal)
CasePreviousTesting: Molecular analysis that excluded intron 22 inversion (HA carrier), tested for intron 22 inversion (confirmed negative), tested for intron 1 inversion (found negative), sequenced the whole coding region of the F8 gene(c.1753-1G>A mutation found)
Gene: F8
Variant: NM_000132.3:c.1753-1G>A
ClinVar: NA
CAID: CA414911340
gnomAD: Not reported
Tags
- DiseaseEntity:FactorVIIIDeficiency
- ParentalTest:Unknown
- Mutation:Large
- inferred_gene_hgnc:3546
- ParentalConfirmation:Paternity
- ClinGen Coag Fac Def VCEP
- InheritancePattern:Xlinked
- Mutation:Splice
- CaseInfo
- ClinVarID:10122
- ParentalTest:Both
- Mutation:Synonymous
- Gene:F8
- HGNC:3546
- InheritancePattern:DeNovoAssertion
- CAID:CA414911340
- Zygosity:CompoundHeterozygous
- inferred_gene_source:hgnc_tag
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
- ClinVarID:439678
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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IVS13 a-2g
Case#: 10
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Inhibitors present
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.2114-2A>G
ClinVar: NA
CAID: CA414904364
gnomAD: NA
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c.1421G>T
Case#: 19
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.1421G>T (p.Gly455Val)
ClinVar: NA
CAID: CA414914381
gnomAD: Not reported
Tags
- DiseaseEntity:FactorVIIIDeficiency
- ParentalTest:Unknown
- inferred_gene_hgnc:3546
- ClinGen Coag Fac Def VCEP
- CAID:CA414914381
- CaseInfo
- Gene:F8
- HGNC:3546
- inferred_gene_source:hgnc_tag
- CAID:CA414904364
- InheritancePattern:NoInheritanceAssertion
- Mutation:Intronic
- Mutation:Missense
- Zygosity:NoZygosityAssertion
Annotators
URL
-
-
www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
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B1 – B13
Case#: B1 - B13
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 17, FVIII:AG = 18, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.940A>G
LegacyVariant:
ClinVar: No
CAID: CA255084
gnomAD:
-
B30. B31
Case#: B30, B31
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 6, FVIII:AG = 10, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.2161A>C, NM_000132.4:c.2161A>T
LegacyVariant:
ClinVar: No
CAID: CA414903738, CA414903741
gnomAD:
-
B73
Case#: B73
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 41, FVIII:AG = 113, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.5123G>A
LegacyVariant:
ClinVar: No
CAID: CA255154
gnomAD:
-
A1
Case#: A1
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 7, FVIII:AG = 25, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.398A>G
LegacyVariant:
ClinVar: No
CAID: CA255061
gnomAD:
Tags
- DiseaseEntity:FactorVIIIDeficiency
- FVIIItesting:Full
- CAID:CA255084
- ParentalTest:Unknown
- inferred_gene_hgnc:3546
- ClinGen Coag Fac Def VCEP
- AssayDiscrepancy:OSA>CSA
- Inhibitor:NotReported
- CAID:CA255061
- CaseInfo
- Gene:F8
- HGNC:3546
- PreviousTesting:None
- CAID:CA255154
- DiseaseSeverity:MildHemophiliaA
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- InheritancePattern:NoInheritanceAssertion
- AssayDiscrepancy:OSA<CSA
- Zygosity:NoZygosityAssertion
- MultipleGeneVariants
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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UQU-HB10
Case#: UQU-HB10, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, Unable to flex knees fully, PTT 45.8
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
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UQU-HB12
Case#: UQU-HB12, Male, 12-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, Unable to flex knees fully, PTT 73.1
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_001313913.1:c.580G>A
ClinVar: NA
CAID: CA414441211
gnomAD: Not reported
-
UQU-HA37
Case#: UQU-HA37, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 49.6, FVIII: 1 to <5% (Moderate), Disabled left knee
CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons
Gene: F8
Variant: NM_000132.3:c.6430-1G>A
ClinVar: NA
CAID: CA414908097
gnomAD: Not reported
-
UQU-HB5
Case#: UQU-HB5, Male, 12-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild, PTT 47.3
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.316G>A (p.Gly106Ser)
ClinVar: 10579 https://www.ncbi.nlm.nih.gov/clinvar/variation/10579/
CAID: CA255329
gnomAD: MAF for Gly106Ser in the Other population 0.0001881<br>https://gnomad.broadinstitute.org/variant/X-138623273-G-A?dataset=gnomad_r2_1
-
Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies
PMID: 28270892
Gene: F8, F9
HGNCID: 3546, 3551
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UQU-HA33
Case#: UQU-HA33, Male, 2-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 99.5, Disabled Right Knee, Severe
CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons
Gene: F8
Variant: NM_000132.3:c.760A>G (p.Asn254Asp)
ClinVar: NA
CAID: CA414918977
gnomAD: Not reported
-
UQU-HB6
Case#: UQU-HB6, Male, 11-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Disabled right knee, PTT 52.2
CasePreviousTesting: Screened for all factor IX exons by capillary sequencing
Gene: F9
Variant: NM_000133.3(F9):c.880C>T (p.Arg294Ter)
ClinVar: 10587 https://www.ncbi.nlm.nih.gov/clinvar/variation/10587/
CAID: CA255344
gnomAD: Not reported
-
UQU-HA34
Case#: UQU-HA34, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: PTT 94, Disabled Left elbow, Severe
CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons
Gene: F8
Variant: NM_000132.3:c.1835G>C (p.Arg612Pro)
ClinVar: NA
CAID: CA414910775
gnomAD: Not reported
Tags
- DiseaseEntity:FactorVIIIDeficiency
- CAID:CA414441211
- CAID:CA414908097
- ParentalTest:Unknown
- Mutation:Nonsense
- ClinGen Coag Fac Def VCEP
- inferred_gene_hgnc:3551
- Gene:F8
- HGNC:3546
- CAID:CA255329
- ClinVarID:10579
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- InheritancePattern:NoInheritanceAssertion
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
- CAID:CA414910775
- Gene:F9
- inferred_gene_hgnc:3546
- HGNC:3551
- CAID:CA255344
- Mutation:Splice
- General
- CaseInfo
- CAID:CA414918977
- ClinVarID:10587
- DiseaseEntity:FactorIXDeficiency
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
16-year-old boy
Case1: Male patient, 16-year-old, Tabriz Iran
DiseaseAssertion: Moderate Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0005261 (Joint hemorrhage), HP:0030137 (Prolonged bleeding following circumcision)
CasePreviousTesting: PCR-SSCP and PCR-CSGE was performed for all 26 exons with exon-intron boundaries of F8. Abnormal PCR product were directly sequenced.
Gene: F8
Variant: NM_000132.3(F8):c.4925A>G (p.Glu1642Gly)
ClinVar: NA
CAID: CA10568060
gnomAD: MAF for Glu1642Gly in the East Asian population 0.0001346 <br /> https://gnomad.broadinstitute.org/variant/X-154157140-T-C
Tags
- CaseInfo
- DiseaseEntity:FactorVIIIDeficiency
- Gene:F8
- HGNC:3546
- ParentalTest:Unknown
- CAID:CA10568060
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- InheritancePattern:NoInheritanceAssertion
- inferred_gene_hgnc:3546
- ClinGen Coag Fac Def VCEP
- Zygosity:NoZygosityAssertion
- FVIIItesting:Partial
Annotators
URL
-
-
onlinelibrary-wiley-com.libproxy.lib.unc.edu onlinelibrary-wiley-com.libproxy.lib.unc.edu
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The patient was born in 1944; at the age of 7 he underwent a tonsillectomy, bled excessively and required a blood transfusion. He had dental extractions when he was 14 and bled for a week afterwards. At 25 he had a birthmark removed from his left shoulder and again bled excessively. At that time two-stage FVIII:C assays were performed and he was diagnosed as having mild haemophilia A with a FVIII:C level of 19%. 3 years later (in 1972) he presented with a large haematoma of the buttock after minor trauma and a two-stage assay reported a FVIII:C level of 11%. Interestingly, his APTT was always normal. In 1977 he had sebaceous cysts removed under the cover of FVIII concentrate. He received further concentrate in 1982 following an injury to his left thigh and 6 weeks later developed hepatitis (in retrospect hepatitis C). He has not had any further bleeding problems. At a recent routine visit his baseline FVIII:C level was checked with our (now routine) one-stage assay and found to be normal. Subsequently on three blood samples taken on different days we obtained the assay results shown in Table I. On the second of these samples the factor VIII antigen was measured by Immunozym ELISA (Techniclone, Dorking) and found to be 82 iu/dl.
Case#: 77 year old male*
DiseaseAssertion:Hemophilia A, mild
FamilyInfo: Brother does not have hemophilia
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The factor VIII coding region was amplified into six overlapping segments from traces of mRNA and from genomic DNA and subsequently sequenced
Gene: F8
Variant: NM_000132.3:c.5918A>T
LegacyVariant:
ClinVar:
CAID: CA414905984
gnomAD:
Tags
- DiseaseEntity:FactorVIIIDeficiency
- FVIIItesting:Full
- ParentalTest:Unknown
- inferred_gene_hgnc:3546
- ClinGen Coag Fac Def VCEP
- CAID:CA414905984
- AssayDiscrepancy:OSA>CSA
- Inhibitor:NotReported
- CaseInfo
- Gene:F8
- HGNC:3546
- PreviousTesting:None
- DiseaseSeverity:MildHemophiliaA
- Mutation:Missense
- inferred_gene_source:hgnc_tag
- InheritancePattern:NoInheritanceAssertion
- Zygosity:NoZygosityAssertion
Annotators
URL
-
-
www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
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Spectrum of F8 Genotype and Genetic Impact on Inhibitor Development in Patients with Hemophilia A from Multicenter Cohort Studies (J-HIS) in Japan
PMID: 33254277
Gene: F8
HGNCID: 3546
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-
onlinelibrary-wiley-com.libproxy.lib.unc.edu onlinelibrary-wiley-com.libproxy.lib.unc.edu
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Usefulness of an in vitro cellular expression model for haemophilia A carrier diagnosis: illustration with five novel mutations in the F8 gene in women with isolated factor VIII:C deficiency
PMID: 25708597
Gene: F8
Disease: Hemophilia A
HGNC:3546
MONDO ID: MONDO:0010602
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Role of chromogenic assays in haemophilia A and B diagnosis
PMID: 29808946
Gene: F8
HGNC: 3546
NoEvidence: This article discusses the role of chromogenic assays in hemophilia A; no case reports in this article
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A genetic analysis of 23 Chinese patients with hemophilia B
PMID: 27109384
Gene: F9
HGNCID: 3551
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-
onlinelibrary.wiley.com onlinelibrary.wiley.com
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Prediction of factor VIII inhibitor development in the SIPPET cohort by mutational analysis and factor VIII antigen measurement
PMID: 29399993
Gene: F8
HGNC: 3546
InsufficientEvidence: This article mentions variants however there are no specific case reports mentioned therefore, insufficient evidence
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Homozygous and heterozygous retinal phenotypes in families harbouring IMPG2 mutations
PMID: 31264916
Gene: IMPG2
HGNC: 18362
Disease: retinitis pigmentosa 56
MONDO: 0013314
InheritancePattern: semi-dominant
Prevalence: Vitelliform macular dystrophy in general is estimated to have a prevalence of 1 in 5,500 (PMID: 27120116).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete, while heterozygous carriers of deleterious variants show incomplete penetrance and variable expressivity.
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journals.asm.org journals.asm.org
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We demonstrate that in CLN5-depleted HeLa cells, the lysosomal sorting receptors sortilin and cation-independent mannose 6-phosphate receptor (CI-MPR) are degraded in lysosomes due to a defect in recruitment of the retromer (an endosome-to-Golgi compartment trafficking component).
ExperimentName: Defective lysosomal sorting receptor degradation in CLN5-depleted HeLa cells
NonPatientCell: HeLa cells (EFO:0001185)
GeneFunction: Lysosomal organization (GO:0007040)
GeneAlteration: CLN5 (or the CLN1 control) was depleted by transient transfection of small interfering RNA (siRNA) into HeLa cells, 48 hrs. before assays were performed.
FunctionalEvidence: CLN5-depleted cells have reduced immunofluorescent signal (Fig. 2K) and reduced expression (Fig. 3A) of two lysosomal sorting receptors; cation-independent mannose 6-phosphate receptor (CI-MPR) and sortilin (Fig. 2K). CLN5-depleted cells also have fragmented TGN46 signal (Fig. 2Q) and increased precursor and intermediate forms of the lysosomal cargo protein cathepsin D (Fig. 3C). These findings are consistent with CI-MPR and sortilin failing to correctly recycle to the Golgi and being degraded in lysosomes instead, possibly due to a defect in a complex called retromer, which returns membrane-associated proteins from the endosome to the Golgi or other cellular compartments. Endosomal signal for the retromer subunit Vps26 is also decreased (Fig. 4E), and both Vps26 and Vps35 are increasingly cytosolic rather than membrane-bound in CLN5-depleted cells (Fig. 6A). These defects are reversed by exogenously expressing CLN5 (Fig. 7B). Rab7 recruitment to the endosome is also defective in CLN5-depleted cells (Figs. 8B,8M). Considering that CLN5 interacts with Rab5 and Rab7 (Fig. 9A), it may serve as a scaffold recruiting Rab7 and the retromer complex to the endosomal membrane, for the purpose of recycling membrane-associated receptors such as sortilin and CI-MPR out of the endosome. Thus, patients with CLN5 loss-of-function variants may have defective recruitment of the retromer complex to the lysosome / endosome and disordered trafficking of membrane proteins out of these compartments as a result.
FAVariants: N/A
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Rp1L1−/− mice display scattered OS disorganization, reduced electroretinogram amplitudes, and progressive photoreceptor degeneration, less severe and slower than in Rp1−/− mice. In single rods of Rp1L1−/−, photosensitivity is reduced, similar to that of Rp1−/−. While individual heterozygotes are normal
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Six Novel Missense Mutations in the LDL Receptor-Related Protein 5 (LRP5) Gene in Different Conditions with an Increased Bone Density
PMID: 12579474
Gene: LRP5
HGNC: 6697
Disease: osteoporosis-pseudoglioma syndrome
MONDO: 0009820
InheritancePattern: autosomal recessive
Prevalence: osteoporosis-pseudoglioma syndrome is estimated to occur in 1 out of every 2,000,000 live births.
Penetrance: The penetrance of the phenotype among homozygous or compound heterozygous cases appears to be complete, while heterozygous carriers of deleterious variants appear to be mildly affected.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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The human U4/U6 snRNP contains 60 and 90kD proteins that are structurally homologous to the yeast splicing factors Prp4p and Prp3p
PMID: 9257651
Gene: PRPF4
HGNC: 17349
Disease: retinitis pigmentosa 70
MONDO: 0014400
InheritancePattern: autosomal dominant
Prevalence: The overall prevalence of retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,500 and 1 in 27,000). The proportion of that incidence made up by the specific form caused by variants in PRPF4 is not clear.
Penetrance: Known disease-causing alleles appear to be incompletely penetrant (PMID: 25383878).
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Retinitis pigmentosa
Case#: Jespersgaard_2019_Patient_167, gender and age not specified, origin likely to be Danish based on cohort
CasePresentingHPOs: N/A
CaseHPOFreeText: The proband has been diagnosed with retinitis pigmentosa, as part of a larger group of generalized non-syndromic retinal dystrophies. Detailed phenotypes are not described.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease.
CaseMethod1: NGS panel
CaseMethod2: N/A
CaseGenotypingMethod: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease. It is not clear whether Sanger sequencing was used to validate the genotyping of this particular case.
Variant: The proband harbors the NM_000440.3(PDE6A):c.627+2T>G variant in the homozygous state.
ClinVar: 636057
gnomAD: The NM_000440.3(PDE6A):c.627+2T>G variant is not found in gnomAD v2.1.1.
VariantEvidence: The NM_000440.3(PDE6A):c.627+2T>G variant disrupts a canonical splice site in intron 2, but does not have experimental confirmation of exon skipping or frameshift.
CaseAddInfo: N/A
CasePMIDs: N/A
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Retinitis Pigmentosa
Case#: Jespersgaard_2019_Patient_162, gender and age not specified, origin likely to be Danish based on cohort
CasePresentingHPOs: N/A
CaseHPOFreeText: The proband has been diagnosed with retinitis pigmentosa, as part of a larger group of generalized non-syndromic retinal dystrophies. Detailed phenotypes are not described.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease.
CaseMethod1: NGS panel
CaseMethod2: N/A
CaseGenotypingMethod: Next-generation sequencing was performed focusing on a targeted panel of 125 genes known to be linked to inherited retinal disease. It is not clear whether Sanger sequencing was used to validate the genotyping of this particular case.
Variant: The proband harbors the NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) variants in the compound heterozygous state.
ClinVar: 636052, 636051
gnomAD: The NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) variants are not found in gnomAD v2.1.1.
VariantEvidence: NM_000440.3(PDE6A):c.1287G>A (p.Trp429Ter) and NM_000440.3(PDE6A):c.1054C>T (p.Gln352Ter) are nonsense variants in exons 10 and 7, respectively. They are predicted to result in nonsense-mediated decay or at least to respectively truncate the C-terminal ~59% or ~50% of the protein product.
CaseAddInfo: N/A
CasePMIDs: N/A
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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In this study, we have generated and characterized Oa1-deficient mice by gene targeting (KO). The KO males are viable, fertile and phenotypically indistinguishable from the wild-type littermates. Ophthalmologic examination shows hypopigmentation of the ocular fundus in mutant animals compared with wild-type. Analysis of the retinofugal pathway reveals a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibres at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE shows the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells, suggests that the giant melanosomes may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.
ExperimentName: Mouse model with hemizygous disruption of the GPR143 ortholog Oa1
NonHumanModel: Mus musculus
GeneAlteration: A hemizygous mouse model of Oa1 knockout was generated by replacement of exon 1 (including the start codon) with a cassette to facilitate selection.
ModelPhenotype: HP:0007894 (Hypopigmentation of the fundus), HP:0025551 (Optic nerve misrouting), Giant melanosomes in retinal pigment epithelial cells
HumanPhenotype: HP:0000639 (Nystagmus), HP:0003593 (Infantile onset), HP:0007663 (Reduced visual acuity), HP:0001361 (Nystagmus-induced head nodding), HP:0000646 (Amblyopia), HP:0000483 (Astigmatism), HP:0000613 (Photophobia), normally pigmented skin and hair, HP:0005592 (Giant melanosomes in melanocytes), HP:0007750 (Hypoplasia of the fovea), HP:0007894 (Hypopigmentation of the fundus), HP:0025551 (Optic nerve misrouting)
ModelEvidence: Although the coat, eye color, and ERG responses of the mice were unaffected, the mice match the human patients in that they exhibit hypopigmentation of the fundus (Fig. 2), optic fiber misrouting at the chiasm, and expansion of individual melanosomes into giant melanosomes within cells of the RPE (Figures 2, 3). The mice match the mode of inheritance from the human patients.
ModelVariant: This model features disruption of Oa1 by knockout, but does not harbor a mutation equivalent to a variant from a human patient.
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Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1
PMID: 11092754
Gene: GPR143
HGNC: 20145
Disease: X-linked recessive ocular albinism
MONDO: 0021019
InheritancePattern: X-linked recessive
Prevalence: Ocular albinism has an estimated prevalence between 1 in 111,000 and 1 in 1,000,000 live births (PMID: 35495622)
Penetrance: Fully penetrant in males, with onset in infancy. Most female carriers appear to be unaffected.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease
PMID: 28041643
GeneName: GNAT2
HGNC: 4394
Disease: achromatopsia 4
MonDO ID: MONDO_0013465
Inheritance: autosomal recessive
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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The significance of diminished IFT-A enrichment at the basal body is unclear. It may affect flagellar assembly kinetics because the mutant cells may not be able to readily utilize large quantities of IFT-A from the flagellar base during flagellar assembly. To test this, ift43Δ136 and ift140 mutants were deflagellated to allow flagellar regeneration. Consistent with a previous report [38], wild type cells and the mutant ift43Δ113 with an intact IFT43 conserved domain rapidly regenerated full length flagella (Fig 6A). The ift43Δ136 and ift140mutant cells could regenerate flagella to their original length but at a slower rate especially in theift140 mutant. Thus, the availability of the proper amount of IFT-A at the flagellar base may play a role in determining the rate of flagellar assembly.
ExperimentName: Chlamydomonas mutant model of IFT140 loss-of-function
NonHumanModel: Chlamydomonas reinhardtii
GeneAlteration: The Ift140 mutant model has disruption of the Chlamydomonas gene by insertion of the paromomycin resistance gene AphVIII between bases 8234 and 8235 of the IFT140 gene (in exon 21 of 28).
ModelPhenotype: The mutant exhibits short flagella due to slower flagellar regeneration as well as absence of IFT43 and IFT122 (IFT-A proteins) from the peri-basal body (shown by immunofluorescent co-localization with α-tubulin).
HumanPhenotype: The human patients exhibit the absence of cilia from fibroblasts
ModelEvidence: The cellular defects of the model in flagellar regeneration/assembly (Figures 6A,6C) parallel the absence of cilia from a high proportion of patient fibroblasts. The model also helps explain this defect by showing the underlying cause; the absence of IFT-A complex components from the peri-basal body region (Figure 5E-5F).
ModelVariant: The model does not feature any of the variants observed in human patients.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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mutations
Case#: Holmberg_Patient_6, male, age 2 at onset and age 13 at death, Dutch origin
CasePresentingHPOs: HP:0003208 (Fingerprint intracellular accumulation of autofluorescent lipopigment storage material), HP:0011463 (Childhood onset), HP:0001268 (Mental deterioration), HP:0000572 (Visual loss), HP:0001251 (Ataxia), HP:0011421 (Death in adolescence), HP:0002540 (Inability to walk), HP:0001250 (Seizure), HP:0000550 (Undetectable electroretinogram), HP:0012018 (EEG with temporal focal spikes), HP:0100952 (Enlarged sylvian cistern), HP:0006855 (Cerebellar vermis atrophy), HP:0002198 (Dilated fourth ventricle), HP:0033725 (Thin corpus callosum), HP:0030891 (Periventricular white matter hyperdensities), HP:0012690 (T2 hypointense thalamus)
CaseHPOFreeText: This patient exhibited the most rapid clinical course from the group of 8 patients. Age of onset was 2, while mental decline was present at age 3 and visual deterioration at age 5. Ataxia, seizures, and abolished electroretinogram were found at age 7. Loss of independent walking occurred at age 8. Posterior EEG spikes in response to low-frequency photic stimuli were observed. T2-weighted images showed increased signal intensity of the periventricular white matter and posterior limb of the capsula interna. The thalamus had abnormally low signal intensity compared to the putamen, caudate nuclei, and white matter.
CaseNotHPOs: HP:0001312 (Giant somatosensory evoked potentials)
CaseNotHPOFreeText: Flash visual evoked potential (fVEP) was found to be normal at age 7.
CasePreviousTesting: Other than clinical phenotype characterization, it is not clear what genotype tests preceded CLN5 sequencing.
CaseMethod1: N/A
CaseMethod2: N/A
CaseGenotypingMethod: Each exon of CLN5 was PCR-amplified and Sanger sequenced in both directions.
Variant: The patient is homozygous for the NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) variant.
ClinVar: 2566 (homozygous)
gnomAD: The maximum allele frequency of the NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) variant is 0.00005437 (within the East Asian population, with no homozygous occurrences). https://gnomad.broadinstitute.org/variant/13-77574715-G-A
VariantEvidence: NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) is a recurring missense variant that has been previously shown to introduce an additional N-glycosylation site within the C-terminal region of CLN5 (PMID:20052765) and to disturb its localization to the lysosome (PMID:20052765).
CaseAddInfo: N/A
CasePMIDs: N/A
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin. Subsequently, both cone and rod photoreceptors degenerate. RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability.
ExperimentName: Mouse knockout model of Rpgr loss-of-function
NonHumanModel: Mus musculus
GeneAlteration: The model has targeted hemizygous (male) or biallelic (female) disruption of the mouse Rpgr gene by insertion of a neomycin resistance cassette to replace exons 4 through 6 with a resistance cassette and generate a null variant.
ModelPhenotype: HP:0030612 (Abnormal retinal morphology on macular OCT), partial mislocalization of blue and green cone opsins to the inner segment, reduced rhodopsin content in the outer segment, HP:0000546 (Retinal degeneration), HP:0030609 (Photoreceptor layer loss on macular OCT), HP:0030610 (Photoreceptor outer segment loss on macular OCT), disorganization of disk membranes, normal connecting cilia morphology, HP:0030483 (Reduced amplitude of dark-adapted bright flash electroretinogram a-wave), HP:0008275 (Abnormal light-adapted electroretinogram),
HumanPhenotype: HP:0007642 (Congenital stationary night blindness), HP:0007994 (Peripheral visual field loss), HP:0000529 (Progressive visual loss), HP:0000365 (Hearing impairment), HP:0002205 (Recurrent respiratory infections), HP:0011109 (Chronic sinusitis), HP:0000388 (Otitis media), HP:0002837 (Recurrent bronchitis), HP:0012263 (Immotile cilia), HP:0005938 (Abnormal respiratory motile cilium morphology)
ModelEvidence: The model has been well-characterized at the ocular level and triggers molecular and photoreceptor cell defects (Figures 4a, 4b, 5, 6, 7a, and 7b) that are consistent with human patient features such as night blindness, central visual field loss, and peripheral visual field loss.
ModelVariant: The model does not feature a variant equivalent to one observed in human patients.
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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P09 GC29680 c.3399T>G p.Tyr1133* Homozygous
Case#: Georgiou_2024_Family_GC29680_Proband_P09, female, reported at age 30 years, family origin reported as from Bangladesh
CasePresentingHPOs: HP:0011003 (High myopia), HP:0030558 (Best corrected visual acuity 0.5 LogMAR)
CaseHPOFreeText: BCVA began at 0.39 logMAR and progressed to 0.54 logMAR.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous genotyping was by either next-generation sequencing panel, whole exome sequencing, or whole genome sequencing, but was unspecified.
CaseMethod1: NGS panel / WES / WGS
CaseMethod2: Sanger sequencing of RBP3
CaseGenotypingMethod: Previous genotyping by either next-generation sequencing panel, whole exome sequencing, or whole genome sequencing was followed by Sanger sequencing of RBP3.
Variant: The individual harbors the NM_002900.3(RBP3):c.3399T>G (p.Tyr1133Ter) variant in the homozygous state.
ClinVar ID: 3675731
gnomAD: The variant is found in gnomAD version 4.1.1 at a frequency of 0.00001098 (1 / 91070) in the South Asian population https://gnomad.broadinstitute.org/variant/chr10-47357112-T-G?dataset=gnomad_r4
VariantEvidence: NM_002900.3(RBP3):c.3399T>G (p.Tyr1133Ter) is a nonsense variant within exon 4 of 4 that is predicted to trigger nonsense-mediated decay.
CaseAddInfo: Potential consanguinity within the proband's family has not been commented on.
CasePMIDs: N/A
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation
PMID: 30628748
Gene: RPE65
HGNC: 10294
Disease: Retinitis pigmentosa 87 with choroidal involvement
MONDO: 0032873
InheritancePattern: Autosomal Dominant
Prevalence: The overall prevalence of Retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of Retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,000 and 1 in 27,000). The prevalence of Retinitis pigmentosa 87 with choroidal involvement is considered to be much lower.
Penetrance: Incomplete penetrance, estimated at 80%
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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A stop sequence at codon 258 exists in a family with adult vitelliform macular dystrophy.
Case#: Wells_1993_Proband_III/5, female, age 44 years at time of first examination, family origin not reported
CasePresentingHPOs: Adult onset HP:0003581, Visual impairment HP:0000505, Subretinal deposits HP:0031528, Abnormal light-adapted single flash electroretinogram HP:0030472.
CaseHPOFreeText: The proband has been diagnosed with adult vitelliform macular dystrophy, with onset in the mid-thirties. Foveal deposits are small, yellow, and at the RPE level.
CaseNotHPOs: Abnormal light-adapted flicker electroretinogram HP:0030473
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing consisted of screening of the RHO locus for disease-causing variants.
CaseMethod1: Sanger sequencing of PRPH2
CaseMethod2: N/A
CaseGenotypingMethod: Previous testing of this family consisted of screening of the RHO locus for variants causing RP, with negative results. Genotyping was performed by Sanger sequencing of the PCRs product to identify the variant.
Variant: The proband harbors the NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) variant in the heterozygous state.
ClinVar ID: 98707
gnomAD: The NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) variant was not found in gnomAD v4.0.0.
VariantEvidence: NM_000322.5(PRPH2):c.774C>A (p.Tyr258Ter) is a nonsense variant in exon 2 of 3 that is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 26% of the protein product.
CaseAddInfo: Although the proband is the only family member genotyped and examined by the authors, her father was confirmed to be similarly affected. Family consanguinity was not reported.
CasePMIDs: N/A
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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deletion
Case#: Xin_Patient_9, sex not mentioned, age 6 at onset, U.S. nationality, Egyptian ethnicity
CasePresentingHPOs: HP:0004302 (Functional motor deficit), HP:0000572 (Visual loss), HP:0001250 (Seizure), HP:0001268 (Mental deterioration), HP:0011463 (Childhood onset), HP:0003736 (Autophagic vacuoles)
CaseHPOFreeText: Motor difficulty was the phenotype at presentation (age 6). Cognitive regression, Seizures, and Visual loss had onset at age 7. EM finding of vacuoles was made specifically in muscle.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing for mutations in the CLN1, CLN2, CLN3, CLN6, and CLN8 had already occurred, using PCR amplification and Sanger sequencing to exclude the possibility of variants in the exons and surrounding noncoding regions. Genome-wide analysis methods were not used, as NCL had already been diagnosed based on clinical phenotypes.
CaseMethod1: PCR amplification of the coding and surrounding non-coding regions of each gene, followed by bidirectional Sanger sequencing
CaseMethod2: as mentioned
CaseGenotypingMethod: CLN5 genotyping was performed by PCR amplification of the four exons and surrounding non-coding regions was performed, followed by bi-directional Sanger sequencing. Synthetic multiplex ligation-dependent probe amplification (MLPA) was then used to calculate average gene dosage ratio for each ratio, in order to detect large deletions.
Variant: The patient is believed to be homozygous for the NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 variant.
ClinVar: 56546 (homozygous)
gnomAD: The NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 variant is absent from gnomAD.
VariantEvidence: NM_006493.4(CLN5):c.772del p.Arg258GlufsTer29 is a frameshift variant that disrupts ~28% of the protein product.
CaseAddInfo: Parents have not been subjected to genotyping, so homozygosity of variants is assumed. This conclusion was supported by failure to detect a deletion, and by family history of consanguinity.
CasePMIDs: N/A
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journals.plos.org journals.plos.org
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We have identified a novel ENU mutant allele of Ift140, which causes a mid-gestation embryonic lethal phenotype in homozygous mutant mice. Mutant embryos exhibit a range of phenotypes including exencephaly and spina bifida, craniofacial dysmorphism, digit anomalies, cardiac anomalies and somite patterning defects.
ExperimentName: Mouse homozygous mutant model of partial IFT140 loss-of-function
NonHumanModel: Mus musculus
GeneAlteration: The Cauli mouse model has biallelic disruption of the mouse Ift140 gene introduced by mutagenesis using N-ethyl-N-nitrosourea. The mutation is a missense change is c.2564T>A (p.Ile855Lys) in Ift140.
ModelPhenotype: HP:0034241 (Prenatal death), HP:0030769 (Exencephaly), HP:0002414 (Spina bifida), HP:0001999 (Abnormal facial shape), HP:0002648 (Abnormality of calvarial morphology), HP:0011297 (Abnormal digit morphology), HP:0001627 (Abnormal heart morphology), HP:0033334 (Abnormal embryonic development, specifically defects in somite patterning), HP:0000528 (Anophthalmia), HP:0001829 (Foot polydactyly), HP:0000194 (Open mouth), HP:0000772 (Abnormal rib morphology), HP:0000896 (Rib exostoses), HP:0001789 (Hydrops fetalis), HP:0001654 (Abnormal heart valve morphology), HP:0010290 (Short hard palate),
HumanPhenotype: HP:0001156 (Brachydactyly), HP:0010579 (Cone-shaped epiphysis), HP:0000556 (Retinal dystrophy), HP:0001591 (Bell-shaped thorax), HP:0000773 (Short ribs), HP:0000107 (Renal cyst), HP:0001252 (Hypotonia), HP:0001263 (Global developmental delay), HP:0001363 (Craniosynostosis), HP:0005054 (Metaphyseal spurs), HP:0010454 (Acetabular spurs), HP:0000083 (Renal insufficiency), HP:0002093 (Respiratory insufficiency), absent cilia in fibroblasts
ModelEvidence: The mode of inheritance in this model matches the biallelic/homozygous mode of inheritance observed in human disease. While the defects in the mouse model are more severe than those of the human patients, shared features include rib cage anomalies (Figure 2), digit anomalies (Figure 4), disruption of eye development (fully penetrant, described in text only), and severe morphological anomalies of the primary cilia in the limb buds (Figure 1G). While the model was generated using a mutagen, it is important to note that the targeted homozygous null mutant in Ift140 recapitulates the features of the model, albeit with enhanced severity. This confirms that the model's mechanism of pathogenicity is incomplete loss of Ift140 function. The localization of Ift140 protein to the base and tip of primary cilia in the limb bud is also consistent with the known function in humans (Figure 5F).
ModelVariant: The model does not feature any of the variants observed in human patients. Instead, the mutation is a missense change, c.2564T>A (p.Ile855Lys) in Ift140. The corresponding residue in human IFT140 is Thr854.
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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shRNA targeting of Kir7.1 inhibited mRNA expression and reduced ERG After demonstrating that Kir7.1 protein is primarily expressed in RPE cells, we sought to determine whether the RPE Kir7.1 channel contributes to the ERG. We delivered a specific shRNA lentiviral particle to the mouse vitreal chamber by micro injection to inhibit Kcnj13 gene expression. Seven days after shRNA injection, eyes were harvested and RPE cells isolated. PCR amplification of Kcnj13 in RPE cells did not reveal a product from the shRNA injected mouse eye (Fig. 3A Lanes 3), whereas in the contralateral eye that received saline injection, a 653 bp band corresponding to the Kcnj13 transcript was present (Fig. 3A Lane 5). Housekeeping gene ß-actin transcript was detected as a 248 bp band in both samples (Fig. 3A Lanes 4 &6). We did not detect either Kir7.1 or actin in negative control experiments (Fig. 3A Lanes 7 & 8). Kir7.1 shRNA inhibition was able to reduce Kcnj13 mRNA expression by an average of 73.62 ± 14.47% (Fig. 3B).
Mouse model based on ERG defects induced by Kcnj13 shRNA injection (packaged in lentiviral particles)
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academic.oup.com academic.oup.com
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A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging
PMID: 15459177
Gene: CLN5
HGNC: 2076
Disease: Ceroid lipofuscinosis, neuronal, 5 (also known as Finnish variant late infantile neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis late infantile Finnish variant, or Finnish vLINCL)
MONDO: 0009745
InheritancePattern: Autosomal Recessive
Prevalence: Unknown, but part of a larger group of NCL disorders with a collective prevalence between 1 in 12,500 (PMID:9662406) and 1 in 100,000 (PMID:23374165)
Penetrance: Fully penetrant, with onset often in the late infantile period but in some cases during early adulthood or even as late as in the 6th decade of life
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www.sciencedirect.com www.sciencedirect.com
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Pedigree AR534; cosegregation of ABCR mutations with retinal disease.
Case#: Shroyer_1999_Proband_AR534-07, female, age 68 years at time of diagnosis, family origin from the United States (Utah or Boston)
CasePresentingHPOs: HP:0000505 (Visual impairment), HP:0000608 (Macular degeneration), HP:0003584 (Late onset)
CaseHPOFreeText: The proband has been diagnosed with exudative age-related macular degeneration.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: The proband and her family members have been genotyped by heteroduplex and SSCP analysis of ABCA4 PCR products, followed by Sanger sequencing-based confirmation.
CaseMethod1: SSCP
CaseMethod2: Sanger sequencing of ABCA4
CaseGenotypingMethod: The proband and her family members have been genotyped by heteroduplex and SSCP analysis of ABCA4 PCR products, followed by Sanger sequencing-based confirmation.
Variant: The proband harbors the NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu) variant in the heterozygous state.
ClinVar ID: 7904
gnomAD: The variant is found in gnomAD v4.1.0 at frequencies of 0.0003059 in the European (non-Finnish) population and 0.001723 in the Ashkenazi Jewish population. https://gnomad.broadinstitute.org/variant/1-94031110-G-A?dataset=gnomad_r4
VariantEvidence: NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu) is a missense variant without functional evidence of a damaging impact on ABCA4.
CaseAddInfo: The proband is the grandmother of four patients with a diagnosis of Stargardt disease. Her 52-year-old daughter carries the same variant but is unaffected (normal fundus).
CasePMIDs: N/A
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Proteoglycan IMPG2 Shapes the Interphotoreceptor Matrix and Modulates Vision
PMID: 32265257
Gene: IMPG2
HGNC: 18362
Disease: retinitis pigmentosa 56
MONDO: 0013314
InheritancePattern: semi-dominant
Prevalence: Vitelliform macular dystrophy in general is estimated to have a prevalence of 1 in 5,500 (PMID: 27120116).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete, while heterozygous carriers of deleterious variants show incomplete penetrance and variable expressivity.
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www.jbc.org www.jbc.org
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A Novel Tissue Inhibitor of Metalloproteinases-3 Mutation Reveals a Common Molecular Phenotype in Sorsby's Fundus Dystrophy
PMID: 10854443
Gene: TIMP3
HGNC: 11822
Disease: Sorsby fundus dystrophy (SFD), also known as Sorsby's fundus dystrophy, Sorsby pseudoinflammatory fundus dystrophy, or hemorrhagic macular dystrophy
MONDO: 0007640
InheritancePattern: Autosomal Dominant
Prevalence: Estimated at 1 in 220,000 (PMID: 28847738)
Penetrance: Fully penetrant, onset between the third and sixth decades of life
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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RP
Case#: Olivier_2021_Family_C_Proband_II:1, female, age 48 years at the time of diagnosis, national origin reported as Spanish
CasePresentingHPOs: HP:0000543 (Optic disc pallor), HP:0007843 (Attenuation of retinal blood vessels), HP:0030329 (Retinal thinning), HP:0007737 (Bone spicule pigmentation of the retina)
CaseHPOFreeText: The proband was diagnosed with moderate retinitis pigmentosa at age 48 years.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: It is not clear whether previous testing methods included systematic genotyping of loci associated with VMD or RP.
CaseMethod1: Screening of IMPG1 using gene panel testing and Sanger sequencing-based confirmation
CaseMethod2: Haplotype analysis using the microsatellite markers D6S1622, D6S456, D6S1589 and D6S251, spanning a 7.2-Mb region surrounding IMPG1.
CaseGenotypingMethod: Genotyping is not entirely clear but has at least included panel-based analysis of the IMPG1 locus, Sanger sequencing-based confirmation, and haplotype analysis of the multiple families harboring the variant.
Variant: The affected family members harbor the NM_001563.4:c.1824+1G>A variant in the heterozygous state.
ClinVar ID: 1240018
gnomAD: This variant is found in gnomAD v2.1.1 at a frequency of 0.00002980 (1 / 33554 alleles total in the Latino / Admixed American population. https://gnomad.broadinstitute.org/variant/6-76660278-C-T
VariantEvidence: NM_001563.4:c.1824+1G>A is an intronic variant disrupting a canonical splice site in intron 13 (of the 17-exon gene), with unknown consequences for IMPG1 splicing.
CaseAddInfo: This family helps establish the incomplete penetrance of the variant, as the patient's carrier mother was clinically asymptomatic with no retinal vessel abnormalities, despite the presence of hard drusen-like deposits in the macula.
CasePMIDs: N/A
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academic.oup.com academic.oup.com
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unusual
Case: Felbor_1995_Family_1_patient_1, gender and age not specified, German-Czech family origin
DiseaseAssertion: Sorsby's fundus dystrophy
FamilyInfo: Family pedigree (from microsatellite-based linkage testing) mapping the disease locus to chr22q13-qter is shown in Figure 1.
CasePresentingHPOs: HP:0030666 (Retinal neovascularization), HP:0007777 (Chorioretinal scar), HP:0000603 (Central scotoma), HP:0000556 (Retinal dystrophy), HP:0007737 (Bone spicule pigmentation of the retina), HP:0000630 (Abnormal retinal artery morphology), HP:0030491 (Choriocapillaris atrophy), HP:0007994 (Peripheral visual field loss), HP:0030469 (Abnormal dark-adapted electroretinogram), HP:0008275 (Abnormal light-adapted electroretinogram)
CaseHPOFreeText: Patients were considered to exhibit early-onset SFD with a mean age of 25. The presenting symptom was central subretinal neovascularisation, which preceded extensive scarring. Second eye involvement generally occurred months later, indicating rapid progression. Retinal dystrophy was reported to be tapetal. Intraretinal arteries were attenuated. Dark adaptation was decreased.
CaseNOTHPOs: N/A
CaseNOTHPOFreeText: N/A
CasePreviousTesting: Genetic linkage testing / genotyping of affected and unaffected family members with three microsatellite markers that were previously associated with SFD and that flank the TIMP3 locus. This was followed by single-stranded conformational polymorphism (SSCP) of all five TIMP3 exons, detecting a mobility shift in exon 5.
CaseGenotypingMethod: Bidirectional Sanger sequencing of exon 5 PCR products from two affected individuals.
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: NM_000362.5(TIMP3):c.536C>G, (p.Ser179Cys) is a missense variant predicted to substitute a new cysteine residue into exon 5.
ClinVar: 12678
gnomAD: Variant is absent from gnomAD.
VariantEvidence: This variant substitutes an additional cysteine residue into the C-terminal region encoded by TIMP3 exon 5. Additional variant evidence is presented in PMID:10854443 and PMID:16223891.
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