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Updated: Jun 21, 2026
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Evaluating the Utility of a New Pathogenicity Predictor for Pediatric Cardiomyopathy
Alyssa L Rippert1, Sarah Trackman2, Danielle Burstein3
1Division of Human Genetics, Children's Hospital of Philadelphia, Pennsylvania, USA.
Insights
CardioBoost scores did not predict major adverse cardiac events in pediatric cardiomyopathy patients. This suggests caution is needed when using this tool for risk stratification in children.
Area of Science:
- Cardiology
- Genetics
- Pediatrics
Background:
- Pediatric cardiomyopathy (CM) contributes to significant childhood morbidity and mortality.
- Genetic factors are key contributors to pediatric CM, but variant interpretation for risk stratification remains challenging.
- Previous studies linked CardioBoost (CB) scores to severe outcomes in adult CM, prompting investigation in pediatric populations.
Purpose of the Study:
- To evaluate the association between CardioBoost (CB) scores and clinical outcomes in pediatric cardiomyopathy patients.
- To determine if CB-classified disease-causing variants can stratify risk for severe clinical outcomes in children with CM.
- To assess the utility of the CardioBoost tool in the pediatric CM population.
Main Methods:
- Retrospective, single-center cohort study of 104 pediatric CM patients evaluated at Children's Hospital of Philadelphia.
- CardioBoost (CB) scores were calculated and categorized (≤0.1, 0.1-0.9, ≥0.9).
- Major adverse cardiac event (MACE) served as the composite endpoint to assess clinical outcomes.
Main Results:
- No significant association was found between CB score categories and the risk of MACE in pediatric CM patients.
- The study included diverse pediatric CM types: 31% dilated CM (DCM), 43% hypertrophic CM (HCM), and 26% other CM.
- The findings indicate limitations in applying adult-derived variant interpretation tools to pediatric populations.
Conclusions:
- The CardioBoost scoring system did not demonstrate significant predictive value for clinical outcomes in pediatric cardiomyopathy.
- This study underscores the ongoing challenges and deficits in interpreting genetic variants for risk stratification in pediatric CM.
- Caution is advised when utilizing the CardioBoost tool for clinical outcome stratification in pediatric CM patients.
Abstract:
Pediatric cardiomyopathy (CM) has significant childhood morbidity and mortality which is caused by both genetic and environmental factors. Previous research has focused on identifying genetic variants in pediatric CM for diagnostic purposes, but not for risk stratification. The current study was modeled after previous work which showed an association between CardioBoost-classified disease-causing variants and an increased risk for severe clinical outcomes in adults with CM to assess if the same association is true in pediatric CM. This was a retrospective, single-center cohort study that evaluated outcomes in pediatric CM patients who were evaluated by the Children's Hospital of Philadelphia (CHOP). CardioBoost (CB) scores were generated for these patients, and scores were categorized as ≤0.1, 0.1-0.9, and ≥0.9. Composite endpoint was freedom from a major adverse cardiac event (MACE). 104 patients were included in the final analysis. 32 (31%) had DCM, 45 (43%) had HCM, and 27 (26%) had other CM. There was no significant association between CB score and clinical outcome in pediatric CM patients. Overall, this study highlights the continued deficits in variant interpretation for pediatric CM. We recommend using caution when applying this tool to stratify clinical outcomes in the pediatric population.
