{ "@context": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/context/doc", "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056", "id": "CG-AC:AC056", "type": "ClinicalActionabilityReport", "metadata": { "schemaLabel": "AC-Sepio.Beta-1 (Unofficial)", "contentVersionId": "30951", "producedAtUTC": "Thu, 10 Sep 2026 19:39:22 -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/AC056/co", "id": "CG-AC:AC056/co", "type": "GeneticCondition", "label": "Familial Hypertrophic Cardiomyopathy" }, "outcome": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ou/Sudden%20cardiac%20death", "id": "CG-AC:AC056/ou/Sudden cardiac death", "type": "Outcome", "label": "Sudden cardiac death" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ou/Morbidity%20due%20to%20left%20ventricular%20outflow%20tract%20obstruction", "id": "CG-AC:AC056/ou/Morbidity due to left ventricular outflow tract obstruction", "type": "Outcome", "label": "Morbidity due to left ventricular outflow tract obstruction" } ], "intervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/intv/Surveillance%20by%20specialists%20to%20guide%20consideration%20of%20implantable%20cardioverter%20defibrillator%20%28ICD%29", "id": "CG-AC:AC056/intv/Surveillance by specialists to guide consideration of implantable cardioverter defibrillator (ICD)", "type": "Intervention", "label": "Surveillance by specialists to guide consideration of implantable cardioverter defibrillator (ICD)" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/intv/Surveillance%20by%20specialists%20to%20guide%20pharmacotherapy", "id": "CG-AC:AC056/intv/Surveillance by specialists to guide pharmacotherapy", "type": "Intervention", "label": "Surveillance by specialists to guide pharmacotherapy" } ], "clinicalActionabilityProfile": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/cap", "id": "CG-AC:AC056/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": "Wed, 22 Jul 2026 00:00:00 -0000", "releaseNum": "3.0.0", "media": "call" }, "evidenceStatements": { "evidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/en/ACMI2893", "id": "CG-AC:AC056/en/ACMI2893", "type": "EvidenceNarrative", "narrative": "Autosomal Recessive", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF000298" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/en/ACMI2894", "id": "CG-AC:AC056/en/ACMI2894", "type": "EvidenceNarrative", "narrative": "Autosomal Dominant", "evidenceDomainTag": "Threat Materialization Chances.Modes of Inheritance", "publication": [ "CG-AC:RF000298" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/en/nh", "id": "CG-AC:AC056/en/nh", "type": "EvidenceNarrative", "narrative": "HCM is a heterogeneous cardiac disease with a diverse clinical presentation and course, presenting in all age groups from infancy to advanced age; however, LVH often becomes apparent during adolescence or young adulthood. The phenotype and clinical condition of HCM changes over lifelong LV remodeling, and cardiovascular events often occur according to the disease stage. A systematic review and meta-analysis of 30 studies found that the average age of HCM onset for individuals with pathogenic variants in sarcomere genes was 36.8 ± 15.5 years. In a cohort of 90 individuals with pathogenic variants in PRKAG2 the average age of onset was 43 ± 16 years. There is equal distribution of HCM by sex, although women are diagnosed less commonly than men. Although HCM was initially thought to be associated with high mortality, it is now recognized that most individuals will be asymptomatic or have a relatively mild course of disease and can achieve normal life expectancy without disability or the necessity for major therapeutic interventions. In some patients, HCM is associated with disease complications that may be profound with the potential to result in debilitating symptoms and/or premature death. An important minority of persons with HCM are at increased risk for SCD most likely related to ventricular tachycardia/ventricular fibrillation. Younger patients with HCM are at higher risk for SCD than older patients. Community-based studies suggest an annual mortality rate in the range of 1-2%. Most HCM-related death at age ≤60 years occur suddenly, while older patients die more often of stroke or heart failure. There are very few data on the natural histories of individuals who carry a pathogenic variant and have no phenotype, but recent studies suggest a benign course for most clinically unaffected carriers.", "evidenceDomainTag": "Nature of the Threat.Natural History", "publication": [ "CG-AC:RF004082", "CG-AC:RF004083", "CG-AC:RF004086", "CG-AC:RF004087", "CG-AC:RF004088", "CG-AC:RF004013", "CG-AC:RF000298", "CG-AC:RF004011", "CG-AC:RF004090" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/en/potgd", "id": "CG-AC:AC056/en/potgd", "type": "EvidenceNarrative", "narrative": "Special note: There are several evidence-based management guidelines for HCM. This report has been prepared with a focus on specific outcome-intervention pairs for HCM predetermined by the actionability working group to be most actionable. As such, this report focuses on sudden cardiac death and left ventricular outflow tract obstruction in individuals with HCM. Therefore, the guidelines included are those focused on these specific outcomes for HCM and are not replicated in their entirety here. Guidelines were only included if they were published within the last 5 years. \n\nHypertrophic cardiomyopathy (HCM) is a common inherited heart disease. The prevalence of unexplained asymptomatic hypertrophy in young adults in the United States has been reported in the range of 1:500. A higher prevalence of 1:200 is estimated when accounting for familial transmission, subclinical cases and pathogenic sarcomere variants. In children, the prevalence is much lower. Symptomatic hypertrophy based on medical claims data has been estimated at <1:3,000 adults in the United States; however, the true burden is much higher when unrecognized disease in the general population is considered. The prevalence of PRKAG2-related HCM is unknown.", "evidenceDomainTag": "Nature of the Threat.Prevalence of the Genetic Disorder", "publication": [ "CG-AC:RF004082", "CG-AC:RF004083", "CG-AC:RF004084", "CG-AC:RF004086", "CG-AC:RF004087", "CG-AC:RF004085", "CG-AC:RF004088", "CG-AC:RF004013" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/en/cf", "id": "CG-AC:AC056/en/cf", "type": "EvidenceNarrative", "narrative": "HCM is typically defined by the presence of unexplained left ventricular hypertrophy (LVH) with a left ventricular (LV) wall thickness of ≥15 mm in adults or an LV wall thickness z-score ≥2 standard deviations above the mean in children. Such LVH occurs in a nondilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed magnitude of increased LV wall thickness. Clinical manifestations of HCM range from asymptomatic LVH to arrhythmias (atrial fibrillation as well as malignant ventricular arrhythmias), thromboembolism, stroke, refractory heart failure, and sudden cardiac death (SCD). Left ventricular outflow tract obstruction (LVOTO) is one of the most characteristic features of HCM. LVOTO is defined as a peak instantaneous Doppler LV outflow tract gradient of ≥30 mmHg. Common symptoms of LVOTO include dyspnea (particularly with exertion), orthostasis, dizziness, light-headedness, syncope, palpitations, and chest pain. Symptoms may be readily provoked by exercise\n\nPathogenic variants in PRKAG2 result in glycogen accumulation within cardiomyocytes and are classically associated with the triad of severe ventricular hypertrophy, electrocardiographic pre-excitation, and conduction system disease.", "evidenceDomainTag": "Nature of the Threat.Clinical Features", "publication": [ "CG-AC:RF004082", "CG-AC:RF004083", "CG-AC:RF004084", "CG-AC:RF004087", "CG-AC:RF004088", "CG-AC:RF004013", "CG-AC:RF000298", "CG-AC:RF004011", "CG-AC:RF004089" ] } ], "tieredEvidenceNarratives": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/CDEC3182", "id": "CG-AC:AC056/ten/CDEC3182", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "Most people with HCM are asymptomatic. HCM is largely underdiagnosed, with only 10-20% identified clinically.", "evidenceDomainTag": "Condition Escape Detection.Chances to Escape Clinical Detection", "publication": [ "CG-AC:RF004082", "CG-AC:RF004086", "CG-AC:RF004085", "CG-AC:RF004011", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/NOI3086", "id": "CG-AC:AC056/ten/NOI3086", "type": "TieredEvidenceNarrative", "narrative": "Cardiac myosin inhibitors are well tolerated and have a good safety profile. In one clinical trial only a small subset of patients developed transient LV systolic dysfunction, which resolved after temporary discontinuation of the drug.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/NOI3085", "id": "CG-AC:AC056/ten/NOI3085", "type": "TieredEvidenceNarrative", "narrative": "Identified interventions include non-invasive surveillance, pharmacotherapy, and possible ICD implantation, which could be associated with moderate risk. ICDs are associated with complications, particularly in young patients, who will require several replacements during their lifetimes. A systematic review and meta-analysis identified 46 studies that reported on post-ICD implantation complications. The overall annual rate of ICD complications was 2% per year. Stratified based on ICD-related complication type, the global rates were as follows: lead displacement 0.98%, lead fracture 0.92%, infection 0.61%, pocket hematoma 0.39%, perforation 0.35%. The overall rate of inappropriate shock/discharges was 3.58% per year and showed a steadily significant decline across time decreasing from 6.01% in 1990 to 2.08% in 2021.", "evidenceDomainTag": "Acceptability of Intervention.Natures of Intervention", "publication": [ "CG-AC:RF004093" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/PGM3115", "id": "CG-AC:AC056/ten/PGM3115", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "HCM is mainly caused by pathogenic variants in sarcomere genes but 5-10% of adults with HCM have variants in non-sarcomere related genes such as PRKAG2.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF004083" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/PGM3113", "id": "CG-AC:AC056/ten/PGM3113", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "One systematic review and meta-analysis included 30 studies with a total of 10,825 patients with HCM. The frequency of pathogenic variants in sarcomere genes was 41%, the top two of which were MYBPC3 (20%) and MYH7 (14%).", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF004090" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/PGM3116", "id": "CG-AC:AC056/ten/PGM3116", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "One study identified pathogenic or likely pathogenic variants in 11 genes associated with HCM in 200,643 individuals in the UK Biobank who underwent whole exome sequencing. The reported prevalence was 1 in 149. Most individuals carried a pathogenic or likely pathogenic variant in MYBPC3 (54%), followed by TNNT2 (20%), MYH7 (17%) and TNNI3 (4%). A frequency of <3% was found in CSRP3, MYL2, TNNC1, TPM1, ACTC1 and MYL3.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF004030" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/PGM3114", "id": "CG-AC:AC056/ten/PGM3114", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review of HCM prevalence in the general population included 213,911 genotyped individuals in 5 studies. Across all cohorts, 1,397 individuals were found to have pathogenic or likely pathogenic variants in sarcomere genes. This indicates a pooled prevalence of 1 in 153 (0.7%) for pathogenic/likely pathogenic variants in the general population.", "evidenceDomainTag": "Threat Materialization Chances.Prevalences of the Genetic Mutation", "publication": [ "CG-AC:RF004097" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/EN3212", "id": "CG-AC:AC056/ten/EN3212", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "4", "narrative": "HCM has variable expressivity; clinical manifestations vary from individual to individual even within the same family. The age at which disease expression occurs in each individual as well as the degree of expression is variable. The time from genetic diagnosis to clinical HCM varies considerably within and between families.", "evidenceDomainTag": "Threat Materialization Chances.Expressivity Notes", "publication": [ "CG-AC:RF004082", "CG-AC:RF000298", "CG-AC:RF004011", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/RR2815", "id": "CG-AC:AC056/ten/RR2815", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "Not provided", "narrative": "Information on relative risk was not available.", "evidenceDomainTag": "Threat Materialization Chances.Relative Risks" }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4774", "id": "CG-AC:AC056/ten/ACPE4774", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "One study reported a cohort of 90 patients with PRKAG2 variants from 47 families. Median age was 42 years and 53% were male. All but two individuals were of European ancestry. The median follow-up period was 6 years. The following findings were reported: \n•Left ventricular hypertrophy (71%)\n•Atrial fibrillation (29%)\n•ICD implantation (24%)\n•Resuscitated SCD in 4 individuals (4.4%)\n•SCD occurred in 3 individuals (3.3%)", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004083" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4779", "id": "CG-AC:AC056/ten/ACPE4779", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "5", "narrative": "One study identified pathogenic or likely pathogenic variants in 11 genes associated with HCM (ACTC1, CSRP3, JPH2, MYBPC3, MYH7, MYL2, MYL3, TNNC1, TNNI3, TNNT2 and TMP1) in 200,643 individuals in the UK Biobank who underwent whole exome sequencing. A total of 1,346 variant carriers were found. The following diagnoses were reported in participant medical records: \n•HCM (2%)\n•Heart failure (3%)\n•Ventricular arrhythmias (1%)\n•Atrial arrhythmias (2%)\n•Cardiac arrest (0.4%)\n•Cardiovascular death (1%)", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004030" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4778", "id": "CG-AC:AC056/ten/ACPE4778", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review and meta-analysis included 30 studies with 10,825 patients with HCM. Patients with pathogenic variants in sarcomere genes (41%) had the following findings: \n•Ventricular tachycardia (23.4%)\n•Atrial fibrillation (21.4%)\n•Syncope (18.3%)\n•Heart failure (17.3%)\n•ICD implantation (23.9%)", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004090" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4777", "id": "CG-AC:AC056/ten/ACPE4777", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review identified 5 studies with adequate genotypic and clinical data to estimate the penetrance of HCM in individuals incidentally discovered to be carrying pathogenic or likely pathogenic variants in sarcomere genes. Overall, the penetrance of HCM in 1,397 individuals with pathogenic or likely pathogenic variants in sarcomere genes was 11%, at a mean age of 56 ±8 years.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004097" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4776", "id": "CG-AC:AC056/ten/ACPE4776", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "3", "narrative": "In children with HCM, larger, population-based studies have shown SCD rates in the region of 1.2-1.5% per year.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/ten/ACPE4775", "id": "CG-AC:AC056/ten/ACPE4775", "type": "TieredEvidenceNarrative", "evidenceSourceTier": "1", "narrative": "A systematic review of SCD in HCM (genetic status unknown) included 98 studies with a total of 70,510 patients and 2,183 SCD events. The average age of the HCM population was 49.1 years, 39% were female. Most patients were adults with a minority of pediatric patients (n=4,229). \n•The overall rate of SCD among adult HCM patients was 0.43%.\n• The rates of reported SCD in patients with HCM have declined over time; 0.73% from 1985-2000 to 0.32% from 2015-2020. \n•Patients ≤ 18 years of age had a significantly higher risk of SCD-more than a 2-fold increase in risk-compared with adult HCM patients aged 19 to 60 years.", "evidenceDomainTag": "Threat Materialization Chances.Penetrances", "publication": [ "CG-AC:RF004098" ] } ], "tieredRecommendations": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7272", "id": "CG-AC:AC056/tr/ACPM7272", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review and meta-analysis of myosin inhibitors in HCM included six randomized controlled trials (RCTs). A total of 826 HCM patients were included with a mean age of 59.8 years in intervention (n=443) vs. 60.9 years in placebo (n=383). All studies had patients having background beta-blocker (BB) or calcium channel blockers (CCB) therapy. The resting left ventricular outflow tract (LVOT) gradient was considerably improved by cardiac myosin inhibitors [MD -57.27]. Other findings included significant differences in the post-Valsalva LVOT gradient [MD -55.86], significantly decreased left ventricle ejection fraction [MD -4.74], functional class improvement (RR 2.21), and significant improvement in a clinical summary score [MD 7.71].", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004096" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7273", "id": "CG-AC:AC056/tr/ACPM7273", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review and meta-analysis of beta blockers in HCM included 21 studies with a total of 775 adult patients. Beta blockers significantly reduced LVOT gradient [SMD: -1.57] and heart rate [SMD: -1.19]. Improvements in functional class, exercise tolerance and symptom burden were consistently reported, although data were subjective and small in scale.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004094" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7277", "id": "CG-AC:AC056/tr/ACPM7277", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The principal role of pharmacological therapy targeted at the dynamic LV obstruction is that of symptom relief because no convincing data are available to suggest that pharmacological therapy alters the natural history of HCM. Because the outflow tract obstruction is remarkable variable throughout daily life, the success of a given medication is determined by the patient’s symptom response and not the measured gradient. Most asymptomatic patients with LVOTO do not require treatment.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7279", "id": "CG-AC:AC056/tr/ACPM7279", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In individuals who are genotype-positive, phenotype-negative for HCM, ICD is not recommended for primary prevention. SCD in genotype-positive, phenotype-negative individuals is rare. No accurate risk predication models for SCD exist in genotype-positive, phenotype-negative individuals currently. In a recent prospective registry, no arrhythmic events in genotype-positive, phenotype-negative individuals (total of 126) were observed, including those exercising vigorously or participating in competitive athletics.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7276", "id": "CG-AC:AC056/tr/ACPM7276", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with HCM without risk factors, ICD placement should not be performed.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7270", "id": "CG-AC:AC056/tr/ACPM7270", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In children less than 16 years of age with HCM and an estimated 5-year risk of SCD ≥6% (based on HCM Risk-Kids score), ICD implantation should be considered. ICD may be considered if the 5-year risk of SCD is ≥ 4%. If the risk of SCD is <4% but the patient also has significant late gadolinium enhancement, left ventricular ejection fraction <50% or LV apical aneurysm an ICD may be considered.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004088" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7278", "id": "CG-AC:AC056/tr/ACPM7278", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "The HCM Risk-SCD calculator is recommended as a method of estimating risk of sudden death at 5 years in patients ≥16 years for primary prevention. Validated pediatric-specific risk prediction models are recommended as a method of estimating risk of sudden death at 5 years in patients <16 years for primary prevention.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7271", "id": "CG-AC:AC056/tr/ACPM7271", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with HCM, a 12-lead electrocardiogram (ECG) and a 24- to 48-hour ambulatory ECG are recommended in the initial evaluation to identify patients who are at risk for SCD and to guide management of arrhythmias.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004085", "CG-AC:RF004011", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7274", "id": "CG-AC:AC056/tr/ACPM7274", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with suspected HCM, a transthoracic echocardiogram (TTE) is recommended in the initial evaluation. Documentation of the maximal wall thickness, cardiac chamber dimensions, systolic function, and the presence of left ventricle (LV) apical aneurysm all inform phenotype severity and SCD risk stratification. Some guidelines recommend cardiovascular magnetic resonance (CMR) imaging for all patients with HCM at initial evaluation while others recommend it only for those with inconclusive TTE. CMR is reasonable in children if TTE imaging windows are limited.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004087", "CG-AC:RF004085", "CG-AC:RF004088", "CG-AC:RF004013", "CG-AC:RF004011", "CG-AC:RF004089", "CG-AC:RF004091" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7275", "id": "CG-AC:AC056/tr/ACPM7275", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "It is recommended that all patients with suspected or established cardiomyopathy undergo systematic evaluation using a multiparametric approach that includes clinical evaluation, pedigree analysis, electrocardiogram (ECG), Holter monitoring, laboratory tests, and multimodality imaging.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004085", "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7268", "id": "CG-AC:AC056/tr/ACPM7268", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "Cardiac myosin ATPase inhibitor (mavacamten) should be considered in addition to a beta-blocker (or verapamil or diltiazem) to improve symptoms in adult patients with resting or provoked LVOTO.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7266", "id": "CG-AC:AC056/tr/ACPM7266", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with obstructive HCM and symptoms attributable to LVOTO, nonvasodilating beta blockers, titrated to effectiveness or maximally tolerated doses, are recommended as first-line therapy. If beta blockers are ineffective or not tolerated, substitution with nondihydropyridine calcium channel blockers (e.g, verapamil, diltiazem) is recommended or disopyramide (in combination with an atrioventricular nodal blocking agent).", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004086", "CG-AC:RF004013", "CG-AC:RF004011", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7264", "id": "CG-AC:AC056/tr/ACPM7264", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review and meta-analysis of ICDs in HCM included 234 studies with a total of 92,500 global patients with HCM (genetic status unknown). The median follow-up duration across the included studies was 4.7 years. The average age of the HCM population was 46.2 years and 37.5% of patients were female. Most studies (192 studies, n=81,257) were conducted in adult patients (age 18-65 years), whereas 22 studies (n=6,825) were conducted in pediatric patients (age <18 years). Based on studies reporting ICD implantation rates (n=130), a total of 12,139 out of 73,883 (16.4%) had an ICD placed with an overall annual ICD implantation rate of 2.79%. The rate of ICD implantation steadily increased over time from an estimated average of 1.09% in 1990 to 4.01% in 2021. The overall annual rate of SCD across the entire studied HCM population was 0.42% per year. A total of 177 studies reported ICD therapy post implantation. The overall rate of appropriate ICD shock/discharge was 3.44% per year. In parallel with the increased rates of ICD implantation, there was a significant decline in the rates of SCD over time (p=0.004). Reported rates of SCD declined from an average of 0.84% in 1990 to 0.31% in 2020, representing ~3-fold decrease.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004093" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7265", "id": "CG-AC:AC056/tr/ACPM7265", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In individuals with a sarcomeric pathogenic variant, ICD implantation should be considered in patients aged 16 years or more with an estimated 5-year risk of SCD of ≥ 4%.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004088" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7263", "id": "CG-AC:AC056/tr/ACPM7263", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with HCM, application of individual clinical judgement is recommended when assessing the prognostic strength of conventional risk marker(s) within the clinical profile of the individual patient, as well as a thorough and balanced discussion of the evidence, benefits, and estimated risks to engage the fully informed patient’s active participation in ICD decision-making. Shared decision-making based on real-world data, individual preferences, beliefs, circumstances and values should inform ICD implantation. ICDs are effective at treating potentially lethal ventricular arrhythmias and preventing SCD.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004086", "CG-AC:RF004011", "CG-AC:RF004089", "CG-AC:RF004092" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7267", "id": "CG-AC:AC056/tr/ACPM7267", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Routine laboratory tests are recommended in all individuals with suspected or confirmed HCM. Recommended laboratory tests include CK, liver function, NT-proBNP, proteinuria, renal function and troponin.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7269", "id": "CG-AC:AC056/tr/ACPM7269", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "It is recommended that all patients with cardiomyopathy have access to multidisciplinary teams with expertise in the diagnosis and management of cardiomyopathies. In patients with HCM, consultations with or referral to a comprehensive or primary HCM center is reasonable to aid in complex disease-related management decisions. Children with a genetic cardiomyopathy generally need lifelong cardiac follow-up. Timely and adequate preparation for transition of care from pediatric to adult services, including joint consultations, is recommended in all adolescents with cardiomyopathy.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACCA3866", "id": "CG-AC:AC056/tr/ACCA3866", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "All patients with LVOTO should avoid dehydration and excess caffeine and alcohol consumption. Avoidance of arterial and venous dilators, digoxin and diuretics should be considered. Some guidelines recommend avoidance of nitroglycerin, amlodipine, nifedipine, angiotensin-converting enzyme/angiotensin II receptor blockers, B-adrenergic receptor agonists and stimulant medications. Some guidelines state that high-intensity sports should be avoided while others state universal restriction from vigorous physical activity or competitive sports is not indicated. Two guidelines state that for asymptomatic adults with HCM without risk factors, participation in high intensity exercise may be reasonable.", "evidenceDomainTag": "Effectiveness of Intervention.Circumstances to Avoid", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004086", "CG-AC:RF004085", "CG-AC:RF004088", "CG-AC:RF004013", "CG-AC:RF004011", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7282", "id": "CG-AC:AC056/tr/ACPM7282", "type": "TieredRecommendation", "evidenceSourceTier": "1", "recommendation": "A systematic review and meta-analysis of pharmacological therapies in HCM included 37 studies with a total of 1,898 patients with obstructive HCM. The average age of participants was 51 years and 57% were male. Pooled analyses showed that disopyramide and myosin inhibitors were associated with the highest reduction in LVOT gradient at rest [MD: -43.5 mmHg and MD: -34.8 mmHg] followed by beta-blockers [MD: -20.7 mmHg] and CCBs [MD: -14.7 mmHg].", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004095" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7281", "id": "CG-AC:AC056/tr/ACPM7281", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "For children with HCM who have ≥1 conventional risk factors, including unexplained syncope, massive LVH, NSVT, or family history of early HCM-related SCD, ICD placement is reasonable after considering the relatively high complication rates of long-term ICD placement in younger patients.", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004086" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7283", "id": "CG-AC:AC056/tr/ACPM7283", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "For adult patients with HCM with ≥1 major risk factors for SCD it is reasonable to offer an ICD. These major risk factors include: \n•Sudden death judged definitively or likely attributable to HCM in ≥ first-degree or close relatives who are ≤50 years of age\n•Massive LVH ≥30 mm in any LV segment\n•≥1 recent episodes of syncope suspected by clinical history to be arrhythmic\n•LV apical aneurysm with transmural scar or LGD\n•LV systolic dysfunction (EF <50%)", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004086", "CG-AC:RF004013", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACPM7280", "id": "CG-AC:AC056/tr/ACPM7280", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In children, adolescents and adults with HCM, a comprehensive, systematic noninvasive SCD risk assessment at initial evaluation should include evaluation of these risk factors: \n•Personal history of cardiac arrest or sustained ventricular arrhythmias\n•Personal history of syncope suspected by clinical history to be arrhythmic\n•Family history in close relative of premature HCM-related sudden death, cardiac arrest, or sustained ventricular arrhythmias\n•Maximal LV well thickness, ejection fraction, LV apical aneurysm\n•Nonsustained ventricular tachycardia (NSVT) episodes on continuous ambulatory ECG monitoring", "evidenceDomainTag": "Effectiveness of Intervention.Patient Managements", "publication": [ "CG-AC:RF004082", "CG-AC:RF004086", "CG-AC:RF004087", "CG-AC:RF004088", "CG-AC:RF004013" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACSU4171", "id": "CG-AC:AC056/tr/ACSU4171", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "Systematic noninvasive SCD risk assessment is recommended every 1 to 3 years or when there is a change in clinical status.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF004082", "CG-AC:RF004086", "CG-AC:RF004088", "CG-AC:RF004013", "CG-AC:RF004011" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACSU4172", "id": "CG-AC:AC056/tr/ACSU4172", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In patients with HCM, a 12-lead ECG and 24- to 48-hour ambulatory ECG are recommended as part of periodic follow-up (every 1 to 3 years).", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004085", "CG-AC:RF004089" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACSU4170", "id": "CG-AC:AC056/tr/ACSU4170", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In children and adults with HCM who have no changes in clinical status or events, repeat TTE is recommended every 1 to 2 years.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF004082", "CG-AC:RF004084", "CG-AC:RF004085" ] }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/tr/ACSU4173", "id": "CG-AC:AC056/tr/ACSU4173", "type": "TieredRecommendation", "evidenceSourceTier": "2", "recommendation": "In individuals who are genotype-positive, phenotype-negative, serial clinical assessment, ECG and echocardiography are recommended at periodic intervals depending on age (1-2 years in children and adolescents, 3-5 years in adults) and change in clinical status. Most physicians continue clinical screening until midlife (approximately 50 years of age) because disease can manifest in adults.", "evidenceDomainTag": "Effectiveness of Intervention.Surveillances", "publication": [ "CG-AC:RF004082", "CG-AC:RF004087", "CG-AC:RF004089" ] } ] }, "evidenceCategory": { "outcomeEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei", "id": "CG-AC:AC056/oei", "type": "EvidenceItem", "natureOfTheThreat": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/nott", "id": "CG-AC:AC056/oei/nott", "type": "EvidenceLine", "prevalenceOfTheGeneticDisorder": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pgd", "id": "CG-AC:AC056/oei/pgd", "type": "EvidenceItem", "keyText": "1-2 in 500", "sourceOfPopulation": "General population", "evidenceNarrative": { "@id": "CG-AC:AC056/en/potgd" } }, "clinicalFeatures": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/cf", "id": "CG-AC:AC056/oei/cf", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC056/en/cf" } }, "naturalHistory": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/nh", "id": "CG-AC:AC056/oei/nh", "type": "EvidenceItem", "evidenceNarrative": { "@id": "CG-AC:AC056/en/nh" } } }, "threatMaterializationChances": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/tmc", "id": "CG-AC:AC056/oei/tmc", "type": "EvidenceLine", "modeOfInheritance": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/moi", "id": "CG-AC:AC056/oei/moi", "type": "EvidenceItem", "keyText": "Autosomal Recessive", "evidenceNarrative": { "@id": "CG-AC:AC056/en/ACMI2893" } }, "prevalenceOfTheGeneticMutation": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pgm", "id": "CG-AC:AC056/oei/pgm", "type": "EvidenceItem", "keyText": "1-2 in 500", "sourceOfPopulation": "General population", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/PGM3115" } }, "penetrance": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4775", "id": "CG-AC:AC056/oei/pe/ACPE4775", "type": "EvidenceItem", "keyText": "< 1 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4775" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4776", "id": "CG-AC:AC056/oei/pe/ACPE4776", "type": "EvidenceItem", "keyText": "1-4 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4776" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4777", "id": "CG-AC:AC056/oei/pe/ACPE4777", "type": "EvidenceItem", "keyText": "5-39 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4777" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4778", "id": "CG-AC:AC056/oei/pe/ACPE4778", "type": "EvidenceItem", "keyText": "5-39 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4778" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4779", "id": "CG-AC:AC056/oei/pe/ACPE4779", "type": "EvidenceItem", "keyText": "1-4 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4779" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/pe/ACPE4774", "id": "CG-AC:AC056/oei/pe/ACPE4774", "type": "EvidenceItem", "keyText": ">= 40 %", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/ACPE4774" } } ], "relativeRisk": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/rr/RR2815", "id": "CG-AC:AC056/oei/rr/RR2815", "type": "EvidenceItem", "keyText": "Unknown", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/RR2815" } } ], "expressivity": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/oei/ex/EN3212", "id": "CG-AC:AC056/oei/ex/EN3212", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/EN3212" } } ] } }, "interventionEvidenceItem": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei", "id": "CG-AC:AC056/iei", "type": "EvidenceItem", "acceptabilityOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/aoi", "id": "CG-AC:AC056/iei/aoi", "type": "EvidenceLine", "natureOfIntervention": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/noi/NOI3085", "id": "CG-AC:AC056/iei/noi/NOI3085", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/NOI3085" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/noi/NOI3086", "id": "CG-AC:AC056/iei/noi/NOI3086", "type": "EvidenceItem", "tieredEvidenceNarrative": { "@id": "CG-AC:AC056/ten/NOI3086" } } ] }, "effectivenessOfIntervention": { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/eoi", "id": "CG-AC:AC056/iei/eoi", "type": "EvidenceLine", "patientManagement": [ { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7269", "id": "CG-AC:AC056/iei/pm/ACPM7269", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7269" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7275", "id": "CG-AC:AC056/iei/pm/ACPM7275", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7275" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7267", "id": "CG-AC:AC056/iei/pm/ACPM7267", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7267" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7274", "id": "CG-AC:AC056/iei/pm/ACPM7274", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7274" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7271", "id": "CG-AC:AC056/iei/pm/ACPM7271", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7271" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7280", "id": "CG-AC:AC056/iei/pm/ACPM7280", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7280" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7278", "id": "CG-AC:AC056/iei/pm/ACPM7278", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7278" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7263", "id": "CG-AC:AC056/iei/pm/ACPM7263", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7263" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7283", "id": "CG-AC:AC056/iei/pm/ACPM7283", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7283" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7265", "id": "CG-AC:AC056/iei/pm/ACPM7265", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7265" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7281", "id": "CG-AC:AC056/iei/pm/ACPM7281", "type": "EvidenceItem", "tieredRecommendation": { "@id": "CG-AC:AC056/tr/ACPM7281" } }, { "@id": "https://actionability.clinicalgenome.org/ac/Adult/api/sepio/doc/AC056/iei/pm/ACPM7270", "id": "CG-AC:AC056/iei/pm/ACPM7270", "type": "EvidenceItem", "tieredRecommendation": { "@id": 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