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Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in
Ana Morales1, Alexander Ing2, Christian Antolik3
1Division of Human Genetics, The Ohio State University, Columbus, Ohio; Invitae Corp., San Francisco, California.
Insights
Standardizing phenotypic data collection for hypertrophic cardiomyopathy (HCM) is crucial for accurate variant interpretation. A consensus on essential data elements was reached, improving diagnostic laboratory practices and patient care.
Area of Science:
- Genetics
- Clinical Diagnostics
- Cardiology
Background:
- Diagnostic laboratories lack standardized phenotypic data collection for variant interpretation.
- This variability hinders accurate classification of genetic variants.
Purpose of the Study:
- To define an essential phenotypic data set for hypertrophic cardiomyopathy (HCM) variant interpretation.
- To standardize diagnostic laboratory requisition forms for HCM.
Main Methods:
- Compiled phenotypic data fields from nine leading cardiomyopathy testing laboratories.
- Conducted a pilot study on 50 HCM cases to assess data harmonization feasibility.
- Surveyed laboratory directors on the adoption of a minimal data set.
Main Results:
- Observed significant divergence in phenotypic data fields across laboratory requisition forms.
- Pilot data showed high completion for demographics (86-98%) but low completion for specific HCM features (24-44%).
- An expert panel identified nine essential data elements for variant classification.
Conclusions:
- A consensus minimal data set for HCM phenotypic information was established.
- Participating laboratories expressed willingness to adopt the standardized data elements.
- Standardization enhances variant interpretation, facilitates data sharing, and improves patient care.
Abstract:
Diagnostic laboratories gather phenotypic data through requisition forms, but there is no consensus as to which data are essential for variant interpretation. The ClinGen Cardiomyopathy Variant Curation Expert Panel defined a phenotypic data set for hypertrophic cardiomyopathy (HCM) variant interpretation, with the goal of standardizing requisition forms. Phenotypic data elements listed on requisition forms from nine leading cardiomyopathy testing laboratories were compiled to assess divergence in data collection. A pilot of 50 HCM cases was implemented to determine the feasibility of harmonizing data collection. Laboratory directors were surveyed to gauge potential for adoption of a minimal data set. Wide divergence was observed in the phenotypic data fields in requisition forms. The 50-case pilot showed that although demographics and assertion of a clinical diagnosis of HCM had 86% to 98% completion, specific phenotypic features, such as degree of left ventricular hypertrophy, ejection fraction, and suspected syndromic disease, were completed only 24% to 44% of the time. Nine data elements were deemed essential for variant classification by the expert panel. Participating laboratories unanimously expressed a willingness to adopt these data elements in their requisition forms. This study demonstrates the value of comparing and sharing best practices through an expert group, such as the ClinGen Program, to enhance variant interpretation, providing a foundation for leveraging cumulative case-level data in public databases and ultimately improving patient care.