Fig. 2. Positional, molecular, and clinical characterization of MYH7 truncating variants (MYH7tv) in left ventricular noncompaction (LVNC) and in the population.

(a) Distribution of MYH7 nontruncating variants demonstrates distinct (though overlapping) enriched clusters in LVNC (blue band) and hypertrophic cardiomyopathy (HCM)²³ (red band). MYH7tv are distributed throughout the transcript in LVNC and population cohorts but with a cluster around the c.732 splice region. (b) Details of the c.732 splice region and associated variants found in LVNC cases. (c) MaxEntScan²⁹ scores for these variants (and the wild type sequence) with the reference exon base at c.732 and the c.732C>T common variant in cis. (d) Pedigree of the Italian family demonstrated segregation of the c.732+1G>A variant with noncompaction and/or varying degrees of myocardial hypertrabeculation. (e) MYH7tv are associated with higher noncompacted to compacted (NC/C) ratios in population cohorts. Maximum NC/C ratios of individuals identified with MYH7tv in population controls not selected for disease (see “Materials and Methods”), compared with age- and sex-matched individuals without MYH7tv drawn from the same populations. Boxplots show the median and interquartile range, red diamond indicates mean and the dashed line shows the diagnostic NC/C ratio of 2.3.