MYL2 non-truncating variants in HCM cohorts

The table below lists the 43 rare (MAF<0.0001 in ExAC) non-truncating MYL2 variants identified in a cohort of 4185 HCM patients (1535 patients from OMGL, 2650 patients from LMM). When this rare variant frequency of 0.01027 is compared with a background population rate of 0.00154, there is a statistically significant case excess of 0.00873 (p<0.0001), which suggests that approximately 37 of these variants may be pathogenic.

Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM

No. Variant (CDS) Variant (Protein) Variant Type Cases (4185)OMGL classLMM class ExAC frequency
1. c.173G>A p.R58Qmissense 7Pathogenic (2)Pathogenic (5)0.000008
2. c.64G>A p.E22Kmissense 5Pathogenic (3)Likely Pathogenic (2)0.000008
3. c.485G>A p.G162Emissense 3Likely Pathogenic (3)0.000000
4. c.170G>A p.G57Emissense 2Likely Pathogenic (2)0.000000
5. c.239C>A p.T80Nmissense 2Likely Pathogenic (2)0.000000
6. c.459G>C p.K153Nmissense 2VUS (2)0.000024
7. c.313G>A p.V105Mmissense 2VUS (2)0.000000
8. c.80A>G p.Q27Rmissense 2VUS (1)Likely Pathogenic (1)0.000000
9. c.260G>C p.G87Amissense 2Likely Pathogenic (2)0.000000
10. c.257T>C p.F86Smissense 2VUS (2)0.000008
11. c.374C>T p.T125Mmissense 1VUS favour benign (1)0.000041
12. c.163G>T p.A55Smissense 1VUS (1)0.000000
13. c.392C>G p.S131Cmissense 1VUS favour pathogenic (1)0.000000
14. c.485_487del p.Gly162delinframe 1VUS (1)0.000000
15. c.193G>A p.E65Kmissense 1Likely Pathogenic (1)0.000000
16. c.275G>T p.G92Vmissense 1Likely Pathogenic (1)0.000000
17. c.428C>T p.P143Lmissense 1VUS (1)0.000024
18. c.119G>A p.R40Kmissense 1VUS (1)0.000000
19. c.84A>T p.E28Dmissense 1VUS favour pathogenic (1)0.000000
20. c.402G>C p.E134Dmissense 1VUS favour pathogenic (1)0.000000
21. c.458A>G p.K153Rmissense 1VUS (1)0.000000
22. c.482A>G p.H161Rmissense 1Likely Pathogenic (1)0.000000
23. c.358C>T p.R120Wmissense 1VUS favour pathogenic (1)0.000000
24. c.142G>T p.D48Ymissense 1VUS favour pathogenic (1)0.000000


1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

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