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 score | Case excess (variant) | De novo variant | ||||
|---|---|---|---|---|---|---|---|
 | no excess |  | 0.6 |  | - |  | - |
| See details below | |||||||
| Cohort (reference) | HCM patients tested | Rare variants | Case Frequency | Significance 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.