| [ |
| { |
| "id": "AITX-00001", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "Eteplirsen", |
| "answer_explanation": "Variant results in deletion of exons 52-63, which is listed as amenable to exon 51 skipping", |
| "difficulty_rationale": "", |
| "sources": ["GeneReviews", "PubMed/Literature"], |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00002", |
| "patient": { |
| "genotype": [ |
| { |
| "gene": "DMD", |
| "transcript": "NM_004006.2", |
| "variant_cdna": "c.10453_10454delinsTA", |
| "variant_protein": "p.(Leu3485Ter)", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "Ataluren", |
| "answer_explanation": "Variant results in a nonsense in exon 74, which is amenable to nonsense readthrough", |
| "difficulty_rationale": "", |
| "sources": [], |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00003", |
| "patient": { |
| "genotype": [ |
| { |
| "gene": "DMD", |
| "transcript": "NM_004006.2", |
| "variant_cdna": "c.70T>C", |
| "variant_protein": "p.(Trp24Arg)", |
| "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: Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Ataluren, or None?", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "None", |
| "answer_explanation": "Results in a missense in exon 2, which is not amenable to nonsense readthrough and is upstream from skippable exons", |
| "difficulty_rationale": "", |
| "sources": [], |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00004", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "Pyridoxine", |
| "answer_explanation": "Missense variants are amenable to pyridoxine treatment", |
| "difficulty_rationale": "", |
| "sources": ["GeneReviews"], |
| "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"] |
| }, |
| { |
| "id": "AITX-00005", |
| "patient": { |
| "genotype": [ |
| { |
| "gene": "AGXT", |
| "transcript": "NM_000030.3", |
| "variant_cdna": "c.33dup", |
| "variant_protein": "p.(Lys12GlnfsTer156)", |
| "zygosity": "homozygous" |
| } |
| ], |
| "clinical_context": "Recurrent nephrocalcinosis and chronic kidney disease" |
| }, |
| "question": { |
| "category": "Established_Targeted", |
| "answer_format": "binary", |
| "prompt": "Is this patient predicted to be responsive to pyridoxine? Answer yes or no.", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "No", |
| "answer_explanation": "Pyridoxine is not effective for patients with null variants", |
| "difficulty_rationale": "", |
| "sources": ["GeneReviews"], |
| "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"] |
| }, |
| { |
| "id": "AITX-00006", |
| "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 generic name.", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "Lumasiran", |
| "answer_explanation": "Lumasiran is approved for patients of all ages whereas Nedosiran is only approved for patients age >9.", |
| "difficulty_rationale": "slight change in patient age changes the answer", |
| "sources": ["GeneReviews"], |
| "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1283/"] |
| }, |
| { |
| "id": "AITX-00007", |
| "patient": { |
| "genotype": [ |
| { |
| "gene": "DDC", |
| "transcript": "NM_001082971.2", |
| "variant_cdna": "c.286G>A", |
| "variant_protein": "p.(Gly96Arg)", |
| "zygosity": "homozygous" |
| } |
| ], |
| "clinical_context": "Global developmental delay" |
| }, |
| "question": { |
| "category": "Established_Targeted", |
| "answer_format": "string_match", |
| "prompt": "What is the youngest age for which a gene therapy is approved for this patient's genetic condition in the united kingdom? Answer with the format \"X months\".", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "18 months", |
| "answer_explanation": "specified on GeneReviews", |
| "difficulty_rationale": "", |
| "sources": ["GeneReviews"], |
| "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK595821/"] |
| }, |
| { |
| "id": "AITX-00008", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "ascorbic acid, desmopressin", |
| "answer_explanation": "specified in management on GeneReviews", |
| "difficulty_rationale": "", |
| "sources": ["GeneReviews"], |
| "citations": ["https://www.ncbi.nlm.nih.gov/books/NBK1244/#eds.Management"] |
| }, |
| { |
| "id": "AITX-00009", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "NCT05402384", |
| "answer_explanation": "search for SLC35A2 on ClinicalTrials.gov returns only 2 trials, 1 of which is upcoming", |
| "difficulty_rationale": "", |
| "sources": ["ClinicalTrials.gov"], |
| "citations": ["https://clinicaltrials.gov/study/NCT05402384"] |
| }, |
| { |
| "id": "AITX-00010", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "No", |
| "answer_explanation": "Exclusion criteria lists hemoglobin <7", |
| "difficulty_rationale": "", |
| "sources": ["ClinicalTrials.gov"], |
| "citations": ["https://clinicaltrials.gov/study/NCT05402384"] |
| }, |
| { |
| "id": "AITX-00011", |
| "patient": { |
| "genotype": [ |
| { |
| "gene": "KCNT1", |
| "transcript": "NM_020822.3", |
| "variant_cdna": "c.2849G>A", |
| "variant_protein": "p.Arg950Gln", |
| "zygosity": "heterozygous" |
| } |
| ], |
| "clinical_context": "early-onset seizures and developmental delays" |
| }, |
| "question": { |
| "category": "Clinical_Trials", |
| "answer_format": "string_match", |
| "prompt": "For which clinical trials evaluating new therapeutics is this patient eligible? Provide a clinical trial ID or answer None.", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "None", |
| "answer_explanation": "Only a natural history study is listed.", |
| "difficulty_rationale": "", |
| "sources": ["ClinicalTrials.gov"], |
| "citations": ["https://clinicaltrials.gov/search?cond=KCNT1"] |
| }, |
| { |
| "id": "AITX-00012", |
| "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 it more likely amenable to treatment with Memantine, L-serine, or Radiprodil", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "L-Serine", |
| "answer_explanation": "Variant is a LOF variant. L-serine is being used for LOF variants whereas the others are being used for GOF variants", |
| "difficulty_rationale": "", |
| "sources": ["PubMed/Literature"], |
| "citations": ["https://academic.oup.com/brain/article/147/5/1653/7611854?login=false"] |
| }, |
| { |
| "id": "AITX-00013", |
| "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": "How many amino acids are coded for by the exon in which this variant occurs? Answer with a number", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "66", |
| "answer_explanation": "visual inspection on Ensembl", |
| "difficulty_rationale": "", |
| "sources": ["Other"], |
| "otherSource": "Ensembl", |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00014", |
| "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 percentage of the total coding transcript for this gene are encoded by the exon in which this variant occurs? Answer with a decimal to nearest tenth.", |
| "date_submitted": "2025-08-01" |
| }, |
| "answer_expected": "0.1", |
| "answer_explanation": "66/660 = 0.1", |
| "difficulty_rationale": "", |
| "sources": ["Other"], |
| "otherSource": "Ensembl", |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00015", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "No", |
| "answer_explanation": "At the end of the last exon, after the main domain", |
| "difficulty_rationale": "", |
| "sources": ["Other"], |
| "otherSource": "Ensembl", |
| "citations": [] |
| }, |
| { |
| "id": "AITX-00016", |
| "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": "2025-08-01" |
| }, |
| "answer_expected": "GRD", |
| "answer_explanation": "GRD, GAP related domain (1198–1549 residues)", |
| "difficulty_rationale": "", |
| "sources": ["PubMed/Literature"], |
| "citations": ["https://www.mdpi.com/2073-4425/13/7/1130#"] |
| } |
| ] |
