GeneticsTier 2Medical Sciences concept

Hypertrophic cardiomyopathy genetics (MYBPC3, MYH7, sarcomeric proteins)

Core concept

Autosomal dominant, sarcomeric protein gene mutations - the most common inherited cardiac disease (~1:500 general population)
MYBPC3 (myosin-binding protein C) and MYH7 (beta-myosin heavy chain) together account for ~70-80% of genotype-positive cases - the two dominant genes
Other sarcomeric genes (TNNT2, TNNI3, TPM1, MYL2/3) are individually much less common
~40-60% of clinically diagnosed HCM has no identifiable pathogenic variant (genotype-negative)

MYBPC3 mutations - often later onset, incomplete penetrance; typically truncating variants -> haploinsufficiency
MYH7 mutations - often earlier onset, more severe phenotype; typically missense variants -> dominant-negative ("poison peptide") effect
TNNT2 (troponin T) mutations - modest hypertrophy but disproportionately high sudden death risk - genotype matters for risk stratification, not wall thickness alone

Cascade genetic testing of first-degree relatives once a pathogenic variant is found in the proband - the main clinical payoff of genetic testing
Genotype-negative HCM - relatives still need clinical screening (ECG/echo), since there is no variant to cascade
Genetic result feeds into (but does not replace) sudden death risk calculators (e.g. HCM Risk-SCD)

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.