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. 2021 May;23(5):589-598.
doi: 10.1016/j.jmoldx.2021.01.014. Epub 2021 Feb 22.

Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel

Ana Morales  1 , Alexander Ing  2 , Christian Antolik  3 , Christina Austin-Tse  4 , Linnea M Baudhuin  5 , Lucas Bronicki  6 , Allison Cirino  7 , Megan H Hawley  2 , Michael Fietz  8 , John Garcia  9 , Carolyn Ho  10 , Jodie Ingles  11 , Olga Jarinova  6 , Tami Johnston  3 , Melissa A Kelly  12 , C Lisa Kurtz  13 , Matt Lebo  14 , Daniela Macaya  15 , Lisa Mahanta  2 , Joseph Maleszewski  16 , Arjun K Manrai  17 , Mitzi Murray  15 , Gabriele Richard  15 , Chris Semsarian  10 , Kate L Thomson  18 , Tom Winder  9 , James S Ware  19 , Ray E Hershberger  20 , Birgit H Funke  14 , Matteo Vatta  21 ; ClinGen Cardiovascular Clinical Domain Working Group; Cardiomyopathy Variant Curation Expert Panel
Affiliations

Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel

Ana Morales et al. J Mol Diagn. 2021 May.

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.

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