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We have previously described two distinct mutations in the beta-myosin heavy chain gene with markedly different clinical presentations and outcome: The 908Leu--&gt;Val mutation was associated with a low disease penetrance and a benign prognosis. In contrast, the 403Arg--&gt;Gln mutation in a Caucasian kindred was associated with a 100% disease penetrance and high incidence of sudden cardiac death. Recently, another mutation, 606Val--&gt;Met, has been reported to be associated with "near normal survival" and offered as evidence for the benign nature of neutral charge substitutions.

circulation

Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations.