MYPN in Hypertrophic Cardiomyopathy (HCM)

Evidence for role of MYPN in HCM

A detailed analysis of the role of non-sarcomeric genes in HCM - incorporating clinical sequencing data from the OMGL and LMM labs, a cohort of over 800 HCM probands from the Royal Brompton Hospital, London and the National Heart Centre, Singapore (sequenced on a broad cardiac NGS panel) and published sequencing, segregation and functional data - has clarified the involvement of MYPN variants in this condition (see our study published in the European Heart Journal for further details).

Based on this analysis, MYPN is classified as having: Functional data only (no genetic evidence)


Case excess (gene)Max LOD scoreCase excess (variant)De novo variant
non-significant- - -
See details below

Cohort (reference)HCM patients testedRare variantsCase FrequencySignificance vs ExAC
20801532 93 0 0.00000 no excess
22286171 484 9 0.01860 p=0.438
28082330 804 12 0.01493 p=0.880
Total 1381 21 0.01521 p=0.731

Summary of the frequency of rare MYPN variants (ExAC frequency < 0.0001) in published cohorts of HCM probands. P-values shown are from Fisher' Exact test compared to rare variants in ExAC (ExAC frequency = 0.01434). Significance is based on multiple testing correction of 31 genes tested (p<0.0016).



References

1. Roddy Walsh, Rachel Buchan, Alicja Wilk, Shibu John, Leanne E. Felkin, Kate L. Thomson, Tang Hak Chiaw, Calvin Chin Woon Loong, Chee Jian Pua, Claire Raphael, Sanjay Prasad, Paul J. Barton, Birgit Funke, Hugh Watkins, James S. Ware, Stuart A. Cook. Defining the genetic architecture of hypertrophic cardiomyopathy: re-evaluating the role of non-sarcomeric genes. Eur Heart J. 2017 doi:10.1093/eurheartj/ehw603.