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To test this, we performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A\/C. Compared with gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal topology are evident, differences in chromatin compartmentalization are limited to a few hotspots that escape segregation to the nuclear lamina and inactivation during cardiogenesis. These regions exhibit up-regulation of multiple noncardiac genes including CACNA1A, encoding for neuronal P\/Q-type calcium channels. Pharmacological inhibition of the resulting current partially mitigates the electrical alterations. 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