- Heterozygous variants in TRIM63 had previously been implicated in cardiomyopathy in humans. However, with the release of large control databases (ExAD and gnomAD) these previously-identified variants were deemed non-disease-causing due to their high population frequencies.
- By diagnostic exome sequencing (DES) we identified a patient with cardiomyopathy harboring biallelic loss of function variants in TRIM63, similar to another previously published patient. These patients, combined with evidence from in-vivo studies of knockout mice as well as in-vitro cellular studies, make a strong case to support the notion that biallelic loss of function variants in TRIM63, rather than heterozygous variants, are the cause of cardiomyopathy in humans.
- DES is a useful tool for identifying not only novel human disease genes but also for clarifying the mutational mechanism of disease.
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