MYH7B – Left Ventricular Non‐Compaction

A homozygous missense variant in MYH7B (c.???, p.Arg890Cys) was identified in an Italian family with left ventricular non‐compaction (LVNC) and segregated with disease; the same p.Arg890Cys change was also found in an unrelated LVNC patient, implicating MYH7B in classical LVNC phenotypes (PMID:23800289).

However, comprehensive transcriptome and proteome analyses demonstrate that MYH7b transcripts undergo non‐productive alternative splicing in mammalian hearts, preventing full‐length protein expression and challenging the mechanistic basis for how MYH7B variants drive LVNC (PMID:34227390).

Key Take-home: Current genetic evidence for MYH7B in LVNC is limited; screening for the p.Arg890Cys variant may be considered in LVNC cases, but functional validation is required to establish pathogenicity.

References

• Orphanet Journal of Rare Diseases • 2013 • Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. PMID:23800289
• Journal of the American Heart Association • 2021 • Nonproductive Splicing Prevents Expression of MYH7b Protein in the Mammalian Heart. PMID:34227390

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