{
  "patient": {
    "genotype": [
      {
        "gene": "AGXT",
        "transcript": "NM_000030.3",
        "variant_cdna": "c.33dup",
        "variant_protein": "p.(Lys12GlnfsTer156)",
        "zygosity": "homozygous"
      }
    ],
    "clinical_context": "7-year-old with recurrent nephrocalcinosis and chronic kidney disease"
  },
  "question": {
    "category": "Established_Targeted",
    "answer_format": "string_match",
    "prompt": "What targeted, genetic therapies are approved for this patient in the US? Provide the alphabetized list of generic names.",
    "date_submitted": "2025-01-01"  
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "CFTR",
        "transcript": "NM_000492.4",
        "variant_cdna": "c.1521_1523del",
        "variant_protein": "p.Phe508del",
        "zygosity": "homozygous"
      }
    ],
    "clinical_context": "A 15-year-old male with a diagnosis of cystic fibrosis presents with chronic sinopulmonary disease characterized by persistent respiratory symptoms and recurrent infections. He also has exocrine pancreatic insufficiency requiring enzyme replacement therapy and exhibits features of male infertility consistent with congenital bilateral absence of the vas deferens (CBAVD)."
  },
  "question": {
    "category": "Established_Targeted",
    "answer_format": "binary",    
    "prompt": "Is the c.1521_1523del (F508del) variant eligible for treatment with Trikafta (elexacaftor/tezacaftor/ivacaftor)? Respond with “Yes” or “No”.",
    "date_submitted": "2024-12-10"  
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "AGXT",
        "transcript": "NM_000030.3",
        "variant_cdna": "c.508G>A",
        "variant_protein": "p.(Gly170Arg)",
        "zygosity": "homozygous"
      }
    ],
    "clinical_context": "Recurrent nephrocalcinosis and chronic kidney disease"
  },
  "question": {
    "category": "Established_Targeted",
    "answer_format": "string_match",
    "prompt": "What targeted, small molecule therapy is available for this patient? Provide the generic name or None.",
    "date_submitted": "2025-07-15"
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "DMD",
        "transcript": "NM_004006.2",
        "variant_cdna": "c.7544_9286del",
        "variant_protein": "p.(Thr2516_Ala3096del)",
        "zygosity": "hemizygous"
      }
    ],
    "clinical_context": "Progressive muscle weakness"
  },
  "question": {
    "category": "Established_Targeted",
    "answer_format": "multiple_choice",
    "prompt": "To which of the following targeted therapies would this variant be most likely amenable: Golodirsen, Viltolarsen, Eteplirsen, Casimersen, Ataluren, or None?",
    "date_submitted": "2025-07-15"
  }
}  

{
  "patient": {
    "genotype": [
      {
        "gene": "COL1A1",
        "transcript": "NM_000088.4",
        "variant_cdna": "c.1678G>A",
        "variant_protein": "p.(Gly560Ser)",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "Joint hypermobility, skin hyperextensibility, and easy bruising."
  },
  "question": {
    "category": "Established_Supportive",
    "answer_format": "string_match",
    "prompt": "What two medications are most established for decreasing bruising? List generic names in alphabetical order.",
    "date_submitted": "2025-01-15"  
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "OTC",
        "transcript": "NM_000531.5",
        "variant_cdna": "c.386G>A",
        "variant_protein": "p.Arg129His",
        "zygosity": "hemizygous"
      }
    ],
    "clinical_context": "3-month-old male infant with hyperammonemia, lethargy, and poor feeding requiring hospitalization shortly after birth. The patient was born at 35 weeks' gestation and was diagnosed with OTC deficiency following genetic testing. Currently on protein-restricted diet, arginine supplementation, and alternative pathway therapy."
  },
  "question": {
    "category": "Clinical_Trials",
    "answer_format": "binary",
    "prompt": "Based on this patient's gestational age at birth and genetic status, do they meet the inclusion criteria for the OTC-HOPE trial (NCT06255782) testing ECUR-506 gene therapy? Answer \"Yes\" or \"No\".",
    "date_submitted": "2025-02-19"  
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "SLC35A2",
        "transcript": "NM_005660.3",
        "variant_cdna": "c.3G>A",
        "variant_protein": "p.Met1Ile",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "Patient with SLC35A2-CDG who is experiencing seizures and global developmental delay"
  },
  "question": {
    "category": "Clinical_Trials",
    "answer_format": "string_match",
    "prompt": "What clinical trial developing a new therapeutic for this condition is recruiting or listed as upcoming/not yet recruiting? Return a clinical trials ID",
    "date_submitted": "2025-07-15"
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "SLC35A2",
        "transcript": "NM_005660.3",
        "variant_cdna": "c.3G>A",
        "variant_protein": "p.Met1Ile",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "seizures and global developmental delay. Age 2 months, Hemoglobin 5, Normal liver labs, Not enrolled in other trials"
  },
  "question": {
    "category": "Clinical_Trials",
    "answer_format": "binary",
    "prompt": "Is this patient eligible for clinical trial NCT05402384? Answer yes or no.",
    "date_submitted": "2025-07-15"
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "GRIN2B",
        "transcript": "NM_000834.5",
        "variant_cdna": "c.2755C>T",
        "variant_protein": "p.Gln919Ter",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "intellectual disability, seizures, and developmental delays"
  },
  "question": {
    "category": "Drug_Development_and_Repurposing",
    "answer_format": "multiple_choice",
    "prompt": "Is this patient's diagnostic genetic variant more likely amenable to treatment with Memantine, L-serine, or Radiprodil?",
    "date_submitted": "2024-05-05"  
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "ANO10",
        "transcript": "NM_018075.5",
        "variant_cdna": "c.289del",
        "variant_protein": "p.(Met97Ter)",
        "zygosity": "homozygous"
      }
    ],
    "clinical_context": "progressive cerebellar ataxia and peripheral neuropathy"
  },
  "question": {
    "category": "Variant_Assessment",
    "answer_format": "numeric_match",
    "prompt": "What proportion of the total coding transcript for this gene is encoded by the exon in which this variant occurs? Answer with a decimal to nearest tenth.",
    "date_submitted": "2024-05-05"
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "KMT2B",
        "transcript": "NM_014727.3",
        "variant_cdna": "c.8079delC",
        "variant_protein": "p.(Ile2694SerfsTer44)",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "childhood-onset generalized dystonia"
  },
  "question": {
    "category": "Variant_Assessment",
    "answer_format": "binary",
    "prompt": "Based on typical prediction rules, is this variant likely to result in nonsense mediated decay? Answer yes or no.",
    "date_submitted": "2024-05-05"
  }
}

{
  "patient": {
    "genotype": [
      {
        "gene": "NF1",
        "transcript": "NM_001042492.3",
        "variant_cdna": "c.3728T>C",
        "variant_protein": "p.(Leu1243Pro)",
        "zygosity": "heterozygous"
      }
    ],
    "clinical_context": "Malignant Peripheral Nerve Sheath Tumor and Pheochromocytoma"
  },
  "question": {
    "category": "Variant_Assessment",
    "answer_format": "multiple_choice",
    "prompt": "In which functional domain does this variant occur? Answer choices: CSRD, TBD, GRD, Sec14-PH, HLR, NLS, SBR.",
    "date_submitted": "2024-05-05"
  }
}