APA
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Jordan, E., Grover, P. L., Parker, P., Cowan, J., Asatryan, B., Ai, T., … Hershberger, R. E. (2026). An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy. Circulation.
Chicago/Turabian
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Jordan, E., Phoenix L. Grover, P. Parker, J. Cowan, B. Asatryan, Tomohiko Ai, Akos Berthold, et al. “An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy.” Circulation (2026).
MLA
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Jordan, E., et al. “An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy.” Circulation, 2026.
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@article{e2026a,
title = {An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy.},
year = {2026},
journal = {Circulation},
author = {Jordan, E. and Grover, Phoenix L. and Parker, P. and Cowan, J. and Asatryan, B. and Ai, Tomohiko and Berthold, Akos and Bronicki, L. and Brown, Emily E. and Celeghin, R. and Edwards, M. and Fan, Judith and James, Cynthia A. and Johnson, Renee and Judge, Daniel P. and Jurgens, S. and Lahrouchi, N. and Lumbers, T. and Mazzarotto, F. and Domingo, A. Medeiros and Murray, B. and Peters, Stacey and Pilichou, K. and Protonotarios, A. and van Spaendonck-Zwarts, K. V. and Syrris, P. and Wang, Jessica J. and Walsh, Roddy and Ware, J. and Hershberger, R. E.}
}
BACKGROUND Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource evaluation, the DCM gene curation expert panel reconvened in 2024-2025 to conduct a reassessment of genes in DCM.
METHODS The Clinical Genome Resource semiquantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories on the basis of strength of published evidence for a DCM phenotype. Previously curated genes were reassessed, and newly reported gene-disease-mode of inheritance (MOI) relationships, termed "curations," were evaluated.
RESULTS Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence: BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, and RPL3L. Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five reevaluated genes from 2019-2020 had clinically significant changes in classification. Except for JPH2, for which curation was modified to separate autosomal dominant and AR MOI curations, clinically significant changes involved upgrades from low- to high-evidence categories (PLEKHM2, PRDM16, TBX20, TNNI3K), demonstrating the robustness of the Clinical Genome Resource gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including 6 newly evaluated genes and 1 new MOI for a previously evaluated gene, MYBPC3-AR; 4 were classified as No Known Disease Relationship, and remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs: JPH2 (AD-Strong, AR-Limited), LDB3 (AD-Limited, AR-Strong), MYBPC3 (AD-Limited, AR-Limited), and TNNI3 (AD- and AR- Strong).
CONCLUSIONS With substantial new evidence, the genetic architecture of DCM has rapidly expanded. This updated assessment of genes reported in DCM yielded 35 high-evidence curations, an increase from 19 only 5 years ago. The results of this evidence-based evaluation process inform clinical interpretation of genetic information in the care of DCM patients and families.