CAV3 in Hypertrophic Cardiomyopathy (HCM)

Evidence for role of CAV3 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 CAV3 variants in this condition (see our study published in the European Heart Journal for further details).

Based on this analysis, CAV3 is classified as having: Functional data only (no genetic evidence)


Case excess (gene)Max LOD scoreCase excess (variant)De novo variant
no excess0.6 - -
See details below

Cohort (reference)HCM patients testedRare variantsCase FrequencySignificance vs ExAC
14672715 146 1 0.00685 p=0.184
25351510 874 0 0.00000 no excess
28082330 804 0 0.00000 no excess
Total 1824 1 0.00055 no excess

Summary of the frequency of rare CAV3 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 = 0.00138). 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.