MYL2 variants in HCM cohorts

The table below lists the 46 rare (MAF<0.0001 in ExAC) protein-altering MYL2 variants identified in a cohort of 4185 HCM patients (1535 patients from OMGL, 2650 patients from LMM). When this rare variant frequency of 0.01099 is compared with a background population rate of 0.00176, there is a statistically significant case excess of 0.00923 (p<0.0001), which suggests that approximately 39 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.260G>C p.G87Amissense 2Likely Pathogenic (2)0.000000
5. c.313G>A p.V105Mmissense 2VUS (2)0.000000
6. c.239C>A p.T80Nmissense 2Likely Pathogenic (2)0.000000
7. c.459G>C p.K153Nmissense 2VUS (2)0.000024
8. c.257T>C p.F86Smissense 2VUS (2)0.000008
9. c.80A>G p.Q27Rmissense 2VUS (1)Likely Pathogenic (1)0.000000
10. c.170G>A p.G57Emissense 2Likely Pathogenic (2)0.000000
11. c.499T>C p.*167Glnext*91nonsense 1VUS (1)0.000000
12. c.184A>T p.K62Xnonsense 1VUS favour pathogenic (1)0.000000
13. c.358C>T p.R120Wmissense 1VUS favour pathogenic (1)0.000000
14. c.193G>A p.E65Kmissense 1Likely Pathogenic (1)0.000000
15. c.142G>T p.D48Ymissense 1VUS favour pathogenic (1)0.000000
16. c.374C>T p.T125Mmissense 1VUS favour benign (1)0.000041
17. c.84A>T p.E28Dmissense 1VUS favour pathogenic (1)0.000000
18. c.392C>G p.S131Cmissense 1VUS favour pathogenic (1)0.000000
19. c.485_487del p.Gly162delinframe 1VUS (1)0.000000
20. c.428C>T p.P143Lmissense 1VUS (1)0.000024
21. c.482A>G p.H161Rmissense 1Likely Pathogenic (1)0.000000
22. c.275G>T p.G92Vmissense 1Likely Pathogenic (1)0.000000
23. c.163G>T p.A55Smissense 1VUS (1)0.000000
24. c.119G>A p.R40Kmissense 1VUS (1)0.000000
25. c.458A>G p.K153Rmissense 1VUS (1)0.000000
26. c.45_46delinsT p.Asn16fsframeshift 1VUS favour pathogenic (1)0.000000
27. c.402G>C p.E134Dmissense 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.

2. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.