{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146", "id": "CG-AC:AC146", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "28304", "producedAtUTC": "Thu, 10 Sep 2026 19:38:53 -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/AC146/co", "id": "CG-AC:AC146/co", "type": "GeneticCondition", "label": "Primary pulmonary hypertension 1" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ou/Deterioration%20of%20pulmonary%20and%20cardiac%20function", "id": "CG-AC:AC146/ou/Deterioration of pulmonary and cardiac function", "type": "Outcome", "label": "Deterioration of pulmonary and cardiac function" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/intv/Annual%20echocardiogram", "id": "CG-AC:AC146/intv/Annual echocardiogram", "type": "Intervention", "label": "Annual echocardiogram" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/intv/Pharmacotherapy", "id": "CG-AC:AC146/intv/Pharmacotherapy", "type": "Intervention", "label": "Pharmacotherapy" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/intv/Avoidance%20of%20exacerbating%20exposures", "id": "CG-AC:AC146/intv/Avoidance of exacerbating exposures", "type": "Intervention", "label": "Avoidance of exacerbating exposures" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/cap", "id": "CG-AC:AC146/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, 14 Mar 2022 00:00:00 -0000", "releaseNum": "1.2.4", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/en/ACMI2706", "id": "CG-AC:AC146/en/ACMI2706", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/en/nh", "id": "CG-AC:AC146/en/nh", "type": "EvidenceNarrative", "narrative": "All ages are affected, but the mean age at diagnosis of PAH has been reported as ranging from 36 to 65 years. Because the symptoms of PAH are nonspecific and develop slowly diagnosis is often delayed for months or even years. It is currently not possible to predict those who will ultimately develop PAH, although women are at increased risk compared to men. Females are twice as likely to be affected as males; however, survival is worse in males than females. Studies suggest that the female predisposition to PAH may be directly related to the effects of the metabolites of estrogen. Before the availability of disease-specific therapy in the mid-1980’s, the median life expectancy at the time of diagnosis was 2.8 years. Current therapy improves clinical function, but has a modest effect on survival.\\n\\nPAH associated with a pathogenic variant in BMPR2 occurs at an earlier age and is associated with more severe and rapidly progressive disease. Data from an individual patient meta-analysis (N=1,550 patients with PAH; 29% with an identified BMPR2 pathogenic variant) found that at diagnosis, individuals with a BMPR2 pathogenic variant were younger (mean age 35.4 years vs. 42 years; p<0.0001) and had a higher mean pulmonary artery pressure and pulmonary vascular resistance, and a lower cardiac index. During a median of 5.4 years of follow up, individuals with a BMPR2 pathogenic variant were more likely to reach the composite outcome of death or lung transplantation (HR: 1.42 (95% CI: 1.15-1.75; p=0.0011) with similar results among men and women.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF000713", "CG-AC:RF000714", "CG-AC:RF000715", "CG-AC:RF000716", "CG-AC:RF000717", "CG-AC:RF000718" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/en/cf", "id": "CG-AC:AC146/en/cf", "type": "EvidenceNarrative", "narrative": "PAH, a subset of pulmonary hypertension (PH), is characterized by widespread obstruction and obliteration of the smallest pulmonary arteries leading to the resistance to blood flow through the lungs. As a result, the right ventricle attempts to compensate by generating higher pressure to maintain pulmonary blood flow, which eventually progresses to heart failure and premature death. Right heart catheterization with a mean pulmonary artery pressure of 25mm Hg or more with a pulmonary artery wedge pressure of 15mm Hg or less is needed to confirm the diagnosis of PAH. \\n\\nThe symptoms of PH are non-specific and mainly related to progressive right ventricular dysfunction. Initial symptoms are typically induced by exertion and may include: shortness of breath, fatigue, weakness, angina, and syncope. Less commonly patients may also describe dry cough and exercise-induced nausea and vomiting. Symptoms at rest occur only in advanced cases. Individuals with PAH are classified into four functional categories by the World Health Organization (WHO FC): class I: no limitation of physical activity, class II: slight limitation of physical activity, class III: marked limitation of physical activity, class IV: inability to care out physical activity without symptoms.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF000713", "CG-AC:RF000714", "CG-AC:RF000715", "CG-AC:RF000716", "CG-AC:RF000718" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/en/potgd", "id": "CG-AC:AC146/en/potgd", "type": "EvidenceNarrative", "narrative": "Estimates of the prevalence of pulmonary arterial hypertension (PAH) range from 15 to 60 cases per million adult population. Estimate of PAH incidence range from 2.4 to 10 cases per million adult population per year. These statistics include individuals with idiopathic, heritable, and drug induced PAH. PAH is inherited in less than 10% of cases. Pathogenic variants in BMPR2 are the most common genetic cause of familial PAH.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF000713", "CG-AC:RF000714", "CG-AC:RF000715", "CG-AC:RF000716", "CG-AC:RF000717" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/REC2032", "id": "CG-AC:AC146/ten/REC2032", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The phenotype is not expressed in all generations, but when expressed, occurs at an earlier age and is associated with more severe and rapidly progressive disease.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF000717" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/EN2870", "id": "CG-AC:AC146/ten/EN2870", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "For those patients who develop PAH the variability in survival across patients is broad, ranging from sudden death to decades (rare).", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/PGM2817", "id": "CG-AC:AC146/ten/PGM2817", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "Heterozygous BMPR2 pathogenic variants account for approximately 75% of familial PAH and up to 40% of apparently sporadic cases. Hereditary transmission has been reported in approximately 6 to 10% of patients with PAH. Pathogenic variants in BMPR2 have been identified in 50-90% of these individuals.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF000714", "CG-AC:RF000715", "CG-AC:RF000717" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/REC2171", "id": "CG-AC:AC146/ten/REC2171", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "The lifetime risk of PAH for males with a BMPR2 pathogenic variant is 14%, for females the risk is 42%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/ACPE4135", "id": "CG-AC:AC146/ten/ACPE4135", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "BMPR2 pathogenic variants have a penetrance of 20-30%.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF000713", "CG-AC:RF000714", "CG-AC:RF000715", "CG-AC:RF000717" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/REC2144", "id": "CG-AC:AC146/ten/REC2144", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "To date, more than 200 families with heritable PAH are known in the US, including 120 families in whom the specific BMPR2 pathogenic variant is known.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/RR2636", "id": "CG-AC:AC146/ten/RR2636", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "No information related to relative risk was identified.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/NOI2870", "id": "CG-AC:AC146/ten/NOI2870", "type": "TieredEvidenceNarrative", "narrative": "The initial screening for PAH may include cardiac imaging including echocardiography. Other universal management may include the avoidance of factors that may increase the likelihood of PAH. For those with signs of PH, right heart catheterization is used for diagnosis. For the minority of patients diagnosed with PAH, treatment can be varied and may eventually progress to supportive care, symptomatic treatment, disease-specific agents, and potentially lung transplantation.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/ten/CDEC2861", "id": "CG-AC:AC146/ten/CDEC2861", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Because the symptoms of heritable PAH are nonspecific and develop slowly, affected individuals often mistakenly attribute their initial symptoms to aging, poor physical conditioning, or being overweight. Some patients report no symptoms, and diagnosis is suspected on an incidental basis because of cardiac findings such as murmur, then supported by echocardiogram. Diagnosis is often delayed for months or even years, in part because heritable PAH is uncommon and thus rarely considered. The time to diagnosis from onset of symptoms may be shorter in familial PAH, perhaps because of heightened familial awareness.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF000713" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACPM5684", "id": "CG-AC:AC146/tr/ACPM5684", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Individuals at risk for PAH should undergo aggressive treatment for any existing conditions that contribute to the development or worsening of PH (e.g., sleep apnea and systemic hypertension).", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF000718" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACCA3410", "id": "CG-AC:AC146/tr/ACCA3410", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "The hypoxia that accompanies high altitude is associated with pulmonary vasoconstriction and PH in susceptible individuals.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACCA3411", "id": "CG-AC:AC146/tr/ACCA3411", "type": "TieredRecommendation", "evidenceSourceTier": "4", "recommendation": "Cocaine, amphetamines, and related compounds causing vasoconstriction, have been anecdotally associated with PH.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACCA3408", "id": "CG-AC:AC146/tr/ACCA3408", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Other medications that have anecdotal suggestion of increased risk of PH, including estrogen compounds used as oral contraceptives or hormone replacement therapy. Anecdotal reports associating pregnancy with onset of PH raise some concern about the risks involved with pregnancy; however, there is no published consensus regarding the best approach to birth control in women with PAH. Because avoidance of exogenous systemic estrogen is desirable, many experts prefer intrauterine devices (IUDs).", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACCA3409", "id": "CG-AC:AC146/tr/ACCA3409", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "Individuals who are at risk for PAH should avoid appetite-suppressant medications as these have been associated with an increased risk of PH.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF000713" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACSU3716", "id": "CG-AC:AC146/tr/ACSU3716", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review of 37 studies involving 4,192 patients that assess the effectiveness of drug treatment for adults with diagnosed PAH found inconclusive evidence regarding mortality reduction. The reviewers note that few deaths were observed in these studies due to their limited duration, leading to wide confidence intervals and lack of statistical power to detect a difference in mortality; however, a consistent direction of effect and demonstrated improvements in other outcomes, including functional and hemodynamic measures, support that a mortality reduction might exist. Increases in 6-minute walk distance (6MWD) ranging from 27.9 meters (95% CI, 10.3 to 45.4) to 39.9 meters (CI, 21.4 to 58.4) were observed in trials of all drug classes when compared with placebo or standard therapy. The reported minimal clinically meaningful difference in 6MWD is 33 meters for individuals with PAH.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000716" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACSU3718", "id": "CG-AC:AC146/tr/ACSU3718", "type": "TieredRecommendation", "evidenceSourceTier": "3", "recommendation": "No approved therapy for PAH has been shown to prevent progression of the underlying pulmonary vascular disease. PAH remains an incurable disease; currently, with clinicians attempt to manage it with pharmacotherapy. The prognosis of PAH is significantly worse in patients with advanced disease, PAH therapies delay clinical worsening and data are accumulating suggesting that early treatment improves long-term outcome.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000715", "CG-AC:RF000718" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/tr/ACSU3717", "id": "CG-AC:AC146/tr/ACSU3717", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Even in the absence of symptoms, individuals known to be at risk for the development of PAH based on the presence of a known pathogenic variant in BMPR2 should undergo monitoring for the development of PAH. The appropriate interval and type of screening has not been established. Recommendations for screening vary from annual echocardiography to ongoing clinical monitoring for the development of symptoms that would signal disease progression and warrant initiation of pharmacotherapy. There is an ongoing longitudinal study that should clarify issues such as optimal screening strategies and predictors of progression to PAH in asymptomatic BMPR2 carriers (NCT01600898).", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF000715", "CG-AC:RF000717", "CG-AC:RF000718" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei", "id": "CG-AC:AC146/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/nott", "id": "CG-AC:AC146/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/pgd", "id": "CG-AC:AC146/oei/pgd", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC146/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/cf", "id": "CG-AC:AC146/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC146/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/nh", "id": "CG-AC:AC146/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC146/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/tmc", "id": "CG-AC:AC146/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/moi", "id": "CG-AC:AC146/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Dominant", "evidenceNarrative": { "@id": "CG-AC:AC146/en/ACMI2706" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/pgm", "id": "CG-AC:AC146/oei/pgm", "type": "EvidenceItem", "keyText": "Unknown", "sourceOfPopulation": "General population", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/REC2144" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/pe/ACPE4135", "id": "CG-AC:AC146/oei/pe/ACPE4135", "type": "EvidenceItem", "keyText": "5-39 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/ACPE4135" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/pe/REC2171", "id": "CG-AC:AC146/oei/pe/REC2171", "type": "EvidenceItem", "keyText": "5-39 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/REC2171" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/rr/RR2636", "id": "CG-AC:AC146/oei/rr/RR2636", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/RR2636" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/ex/EN2870", "id": "CG-AC:AC146/oei/ex/EN2870", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/EN2870" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/oei/ex/REC2032", "id": "CG-AC:AC146/oei/ex/REC2032", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/REC2032" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei", "id": "CG-AC:AC146/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/aoi", "id": "CG-AC:AC146/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/noi/NOI2870", "id": "CG-AC:AC146/iei/noi/NOI2870", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/NOI2870" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/eoi", "id": "CG-AC:AC146/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/pm/ACPM5684", "id": "CG-AC:AC146/iei/pm/ACPM5684", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACPM5684" } } ], "circumstanceToAvoid": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/cta/ACCA3409", "id": "CG-AC:AC146/iei/cta/ACCA3409", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACCA3409" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/cta/ACCA3411", "id": "CG-AC:AC146/iei/cta/ACCA3411", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACCA3411" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/cta/ACCA3408", "id": "CG-AC:AC146/iei/cta/ACCA3408", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACCA3408" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/cta/ACCA3410", "id": "CG-AC:AC146/iei/cta/ACCA3410", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACCA3410" } } ], "surveillance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/su/ACSU3717", "id": "CG-AC:AC146/iei/su/ACSU3717", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACSU3717" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/su/ACSU3718", "id": "CG-AC:AC146/iei/su/ACSU3718", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACSU3718" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/su/ACSU3716", "id": "CG-AC:AC146/iei/su/ACSU3716", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC146/tr/ACSU3716" } } ] }, "conditionEscapeDetection": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/ced", "id": "CG-AC:AC146/iei/ced", "type": "EvidenceLine", "chanceToEscapeDetection": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC146/iei/cted/CDEC2861", "id": "CG-AC:AC146/iei/cted/CDEC2861", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC146/ten/CDEC2861" } } ] } } }, "references": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/RF000713", "id": "CG-AC:RF000713", "type": "Publication", "publicationType": "GeneReview", "citation": "ED Austin, JE Loyd, JA Phillips. 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