{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016", "id": "CG-AC:AC1016", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "29731", "producedAtUTC": "Thu, 10 Sep 2026 19:39:10 -0000", "note": "DISCLAIMER: The SEPIO-inspired schema presented here is an initial prototype for Clinical Actionability curation summaries and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema." }, "description": "JSON-LD representation of ClinGen Actionability Stage 2 report modeled with SEPIO. The hierarchically structured document will include:\n1. Contextual & topic information, such as the **conditions/diseases** and the **genes**.\n2. Categorized **evidence narratives**, with references.\n\t* This content corresponds to the texts within the *Actionability Summary Report*\n4. **Outcome & Intervention** pairs, with **consensus scoring** in 5 dimensions:\n\t1. Outcome Severity\n\t2. Outcome Likelihood\n\t3. Intervention Effectiveness\n\t4. Nature of the Intervention\n\t5. Total (Overall) Score\n\n*( Note: The summary report does not include the **Screening Survey** which led to preparation of the actionability report. )", "condition": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/co", "id": "CG-AC:AC1016/co", "type": "GeneticCondition", "label": "Medium-chain acyl coenzyme A dehydrogenase deficiency" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ou/Morbidity%20and%20mortality%20associated%20with%20metabolic%20decompensation", "id": "CG-AC:AC1016/ou/Morbidity and mortality associated with metabolic decompensation", "type": "Outcome", "label": "Morbidity and mortality associated with metabolic decompensation" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/intv/Metabolic%20management%20%28dietary%20management%20and%20illness%20protocols%29", "id": "CG-AC:AC1016/intv/Metabolic management (dietary management and illness protocols)", "type": "Intervention", "label": "Metabolic management (dietary management and illness protocols)" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/cap", "id": "CG-AC:AC1016/cap", "type": "Assertion", "assertionMethod": "The ClinGen AWG developed a standardized protocol to generate evidence-based profiles of clinical actionability of genes and associated disorders in the form of summary reports and semiquantitative metric (SQM) scores.", "releaseDate": "Mon, 16 Oct 2023 00:00:00 -0000", "releaseNum": "1.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/en/ACMI2803", "id": "CG-AC:AC1016/en/ACMI2803", "type": "EvidenceNarrative", "narrative": "Autosomal Recessive", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF002852", "CG-AC:RF002854", "CG-AC:RF002855", "CG-AC:RF002851" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/en/potgd", "id": "CG-AC:AC1016/en/potgd", "type": "EvidenceNarrative", "narrative": "Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is the most common inborn error of metabolism and occurs in an estimated 5.3 (99% CI: 4.1-6.7) per 100,000 births. MCAD deficiency is prevalent in individuals of (especially northern) European descent. In the US, prevalence ranges from 1/13,000 to 1/19,000 live births. Native Americans may have a prevalence similar to northern Europeans (1/7500 live births). Prevalence is similar among newborns of Hispanic, Black, and Middle Eastern origin (1/23,000 live births). Estimates for incidence across the world are 1/51,000 in Japan, 1/18,000 in Saudi Arabia, 1/263,500 in Taiwan, 1/19,000 in New South Wales of Australia, 1/4900 in northern Germany, 1/24,900 in Austria, 1/23,000 in central Italy, and 1/23,400 in Canada.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF002852", "CG-AC:RF002853", "CG-AC:RF002854", "CG-AC:RF002855", "CG-AC:RF002851" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/en/nh", "id": "CG-AC:AC1016/en/nh", "type": "EvidenceNarrative", "narrative": "Children with MCAD deficiency appear normal at birth and, if not identified through newborn screening, typically have the first acute episode between age 3 and 24 months, although presentation as late as adulthood is possible. Late-onset presentations have been described in adults after prolonged fasting, including after fasting for surgery, or with alcohol intoxication, often with fatal results. Infants and young children with MCAD deficiency are at a greater risk of metabolic decompensation than older children and adults. Prognosis in infants and young children is excellent once the diagnosis is established and frequent feedings are instituted to avoid prolonged periods of fasting. MCAD deficiency can manifest with sudden and unexpected death, even as late as in adulthood.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF002852", "CG-AC:RF002853", "CG-AC:RF002855", "CG-AC:RF003627" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/en/cf", "id": "CG-AC:AC1016/en/cf", "type": "EvidenceNarrative", "narrative": "MCAD is an enzyme involved in fatty acid-β oxidation. An individual with MCAD deficiency is at risk of metabolic decompensation when their energy needs are not met with exogenous sources and have to rely on stored fat, such as during prolonged fasting or periods of higher energy demand. Clinical symptoms in a previously apparently healthy individual with MCAD deficiency include hypoketotic hypoglycemia and nausea or vomiting that may progress to lethargy, seizures, coma, and even sudden death. Symptoms may be triggered by a common illness, fasting, excessive drug or alcohol intake, diarrhea, or vomiting and can progress to seizures or coma within 1-2 hours of onset; on occasion, seizures or coma may be the presenting sign. Hepatomegaly and liver disease are often present during an acute episode. Uncontrolled metabolic decompensation can increase the risk of neurological findings secondary to brain injury (e.g. loss of developmental milestones) and chronic muscular weakness.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF002852", "CG-AC:RF002853", "CG-AC:RF002854", "CG-AC:RF002855", "CG-AC:RF002851", "CG-AC:RF002856", "CG-AC:RF002857", "CG-AC:RF003627" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/PGM2958", "id": "CG-AC:AC1016/ten/PGM2958", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "More than 98% of cases of MCAD deficiency have a pathogenic variant in ACADM, with the c.985A>G variant accounting for between 56-91% of cases.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/PGM2956", "id": "CG-AC:AC1016/ten/PGM2956", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "A recent newborn screening study in Denmark estimated the carrier frequency of c.985A>G as 1/105.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF002860" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/PGM2957", "id": "CG-AC:AC1016/ten/PGM2957", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The carrier frequency of c.985A>G, the most common variant, is between 1/40 and 1/100 in northern Europeans, suggestive of a founder effect. A similar prevalence has been observed among Portuguese with Roma ancestry and Native Americans of California.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/EN3042", "id": "CG-AC:AC1016/ten/EN3042", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Some individuals with MCAD deficiency may remain asymptomatic, and some individuals with a “milder” biochemical phenotype can still develop life-threatening symptoms.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/ACPE4450", "id": "CG-AC:AC1016/ten/ACPE4450", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "A case series of 14 individuals affected with MCAD deficiency who presented in adulthood (age range 16 to 45 years) reported a 50% mortality rate in acutely presenting cases and a 29% mortality rate overall. Mortality in the infantile cases is approximately 25%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF003627" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/ACPE4451", "id": "CG-AC:AC1016/ten/ACPE4451", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "Newborn screening followed by confirmatory variant analysis of 519,350 newborns in Denmark estimates the incidence of MCAD deficiency as 1/8954. This estimate is four times higher than the incidence of 1/39,691 of clinically presenting cases during the 10-year period prior to initiation of newborn screening. The discrepancy was explained by both a difference in variant spectrum, with the screened population having high numbers of variants associated with a milder biochemical phenotype, as well as a reduced penetrance of 50% of the common c.985A>G variant.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002860" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/ACPE4452", "id": "CG-AC:AC1016/ten/ACPE4452", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "If the diagnosis of MCAD deficiency has not been previously established, at least 18% and up to 25% of affected individuals die during their first metabolic crisis.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/NOI2982", "id": "CG-AC:AC1016/ten/NOI2982", "type": "TieredEvidenceNarrative", "narrative": "Interventions identified for MCAD deficiency include avoidance of fasting, carnitine supplementation, and regular monitoring. Children with MCAD deficiency are at risk for obesity after initiation of treatment, likely due to the frequency of feeding. The cost of long-term supplementation with carnitine could be significant. Furthermore, while no severe untoward effects of L-carnitine have been reported in individuals with MCAD deficiency, some individuals have complained about nausea, diarrhea, abdominal pain, and a fishy odor at higher doses.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/CDEC3010", "id": "CG-AC:AC1016/ten/CDEC3010", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Sudden and unexpected death can be the first manifestation and may occur as late as adulthood.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/ten/CDEC3011", "id": "CG-AC:AC1016/ten/CDEC3011", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Most children with MCAD deficiency are diagnosed through newborn screening. However, affected children have often been misdiagnosed as having Reye syndrome or episodic hypoglycemic coma.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF002852", "CG-AC:RF002853" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6406", "id": "CG-AC:AC1016/tr/ACPM6406", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Pregnant women should receive supplemental carnitine to account for reduced plasma free carnitine levels during pregnancy, though free carnitine may still not reach pre-pregnancy levels. Intravenous glucose should be started as soon as labor begins and continued until the patient has adequate oral intake and can maintain normoglycemia.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6404", "id": "CG-AC:AC1016/tr/ACPM6404", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Individuals should be provided with an emergency protocol/letter to carry at all times. They should be strongly advised to seek medical attention if the individual with MCAD deficiency has an acute illness accompanied by poor intake, vomiting, and/or lethargy. The letter should contain patient identifiers, description of the disorder, emergency treatment protocol, and contact information for the metabolic specialist.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6408", "id": "CG-AC:AC1016/tr/ACPM6408", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Low-dose L-carnitine supplementation is recommended when carnitine levels are below the normal range. Individuals with MCAD deficiency may develop a secondary carnitine deficiency as excess medium chain fatty acids bind to free carnitine and are excreted.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6407", "id": "CG-AC:AC1016/tr/ACPM6407", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Immediate attention and therapy during an acute crisis are key to preventing sudden death. Patients should be assessed and treated aggressively for the precipitant of the metabolic decompensation (e.g., dehydration, fever, infection). Treatment is aimed at reversal of catabolism and prevention of hypoglycemia by giving simple carbohydrates by mouth (e.g., glucose tablets or sweetened, non-diet beverages) or intravenous fluids.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002853", "CG-AC:RF002854", "CG-AC:RF002856", "CG-AC:RF002857", "CG-AC:RF002858" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6405", "id": "CG-AC:AC1016/tr/ACPM6405", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Careful monitoring during trauma and injury is important given increased caloric needs and the risk of decreased intake due to pain and possible alteration in mental state.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6402", "id": "CG-AC:AC1016/tr/ACPM6402", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "There is a risk of metabolic decompensation during surgery, particularly if catabolism is precipitated by fasting and surgery. It is important to minimize catabolism by providing adequate amounts of carbohydrate (orally or intravenously) prior to and during surgery. Operations should be postponed, if possible, in children who are unwell.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854", "CG-AC:RF002859" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6403", "id": "CG-AC:AC1016/tr/ACPM6403", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The mainstay for prevention of primary manifestations in asymptomatic patients with MCAD deficiency is avoidance of prolonged fasting. Infants and children require frequent feedings, with maximum “safe fasting times” of 4-12 hours depending on age. The times are based on the few single patient reports of controlled fasting studies in infants and the feeding practices that have proven successful in avoiding symptomatic episodes in screened populations elsewhere in the world. Older children and teenagers should continue to eat regularly and avoid prolonged overnight fasts by having a starchy bedtime snack and not to miss or have a late breakfast. Adults should continue to avoid fasting and eat a heart-healthy, age appropriate diet. Prolonged and/or intense exercise should be \"covered\" with adequate carbohydrate intake and hydration.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002854", "CG-AC:RF002858" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6401", "id": "CG-AC:AC1016/tr/ACPM6401", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "To establish the extent of disease in an asymptomatic individual with a diagnosis of MCAD deficiency, the following evaluations are recommended:\n• Plasma acylcarnitine, and free and total carnitine analyses\n• Urine acylglycine and organic acid analyses\n• Consultation with a biochemical geneticist, clinical geneticist, and/or genetic counselor.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACPM6409", "id": "CG-AC:AC1016/tr/ACPM6409", "type": "TieredRecommendation", "evidenceSourceTier": "Not provided", "recommendation": "The American College of Medical Genetics and Genomics (ACMG) has developed an ACT sheet to help clinical decision-making following newborn screening: https://www.acmg.net/PDFLibrary/C8-C6-C10.pdf", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACSU3955", "id": "CG-AC:AC1016/tr/ACSU3955", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Regular surveillance should include assessment of anthropometrics, blood carnitine, and diet.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/REC3103", "id": "CG-AC:AC1016/tr/REC3103", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Exercise studies in individuals with MCAD deficiency have had mixed results on the effects of supplementation, with some showing improved exercise tolerance and increased carnitine concentrations in muscle and plasma while others have shown no improvement in exercise tolerance or reduction of fatty acid oxidation rates. Carnitine supplementation has also shown no improvement in detoxification of medium-chain fatty acids or response to fasting.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACCA3663", "id": "CG-AC:AC1016/tr/ACCA3663", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Artificial sweeteners should be avoided.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002855" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACCA3665", "id": "CG-AC:AC1016/tr/ACCA3665", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Aspirin has been demonstrated to exacerbate MCAD deficiency by increasing mitochondrial fatty acid oxidation and long-chain fatty acid flux, and inhibiting peroxisomal fatty acid oxidation, which normally serves as a lipitoxic buffer.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACCA3664", "id": "CG-AC:AC1016/tr/ACCA3664", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Popular high-fat/low-carbohydrate diets and weight loss diets that recommend fasting are not appropriate in MCAD deficiency.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002854" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACCA3662", "id": "CG-AC:AC1016/tr/ACCA3662", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Individuals should avoid infant formulas, coconut oil, and other manufactured foods that contain medium-chain triglycerides as the primary source of fat.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002852" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/tr/ACCA3661", "id": "CG-AC:AC1016/tr/ACCA3661", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Individuals need to be informed that drinking large amounts of alcohol is dangerous. Alcohol intake needs to be limited and must always be taken in combination with food.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF002858" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei", "id": "CG-AC:AC1016/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/nott", "id": "CG-AC:AC1016/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/pgd", "id": "CG-AC:AC1016/oei/pgd", "type": "EvidenceItem", "keyText": "1-2 in 50000", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC1016/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/cf", "id": "CG-AC:AC1016/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1016/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/nh", "id": "CG-AC:AC1016/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC1016/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/tmc", "id": "CG-AC:AC1016/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/moi", "id": "CG-AC:AC1016/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Recessive", "evidenceNarrative": { "@id": "CG-AC:AC1016/en/ACMI2803" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC1016/oei/pgm", "id": "CG-AC:AC1016/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General 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