MYL2 variants in HCM cohorts

The table below lists the 35 rare (MAF<0.0001 in ExAC) protein-altering MYL2 variants identified in a cohort of 2650 HCM patients. When this rare variant frequency of 0.01321 is compared with a background population rate of 0.00176, there is a statistically significant case excess of 0.01145 (p<0.0001), which suggests that approximately 30 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 (2650)LMM class ExAC frequency
1. c.173G>A p.R58Qmissense 5Pathogenic0.000008
2. c.485G>A p.G162Emissense 3Likely Pathogenic0.000000
3. c.260G>C p.G87Amissense 2Likely Pathogenic0.000000
4. c.313G>A p.V105Mmissense 2VUS0.000000
5. c.239C>A p.T80Nmissense 2Likely Pathogenic0.000000
6. c.64G>A p.E22Kmissense 2Likely Pathogenic0.000008
7. c.459G>C p.K153Nmissense 2VUS0.000024
8. c.170G>A p.G57Emissense 2Likely Pathogenic0.000000
9. c.184A>T p.K62Xnonsense 1VUS favour pathogenic0.000000
10. c.358C>T p.R120Wmissense 1VUS favour pathogenic0.000000
11. c.193G>A p.E65Kmissense 1Likely Pathogenic0.000000
12. c.142G>T p.D48Ymissense 1VUS favour pathogenic0.000000
13. c.374C>T p.T125Mmissense 1VUS favour benign0.000041
14. c.84A>T p.E28Dmissense 1VUS favour pathogenic0.000000
15. c.392C>G p.S131Cmissense 1VUS favour pathogenic0.000000
16. c.428C>T p.P143Lmissense 1VUS0.000024
17. c.482A>G p.H161Rmissense 1Likely Pathogenic0.000000
18. c.275G>T p.G92Vmissense 1Likely Pathogenic0.000000
19. c.80A>G p.Q27Rmissense 1Likely Pathogenic0.000000
20. c.163G>T p.A55Smissense 1VUS0.000000
21. c.119G>A p.R40Kmissense 1VUS0.000000
22. c.45_46delinsT p.Asn16fsframeshift 1VUS favour pathogenic0.000000
23. c.402G>C p.E134Dmissense 1VUS favour pathogenic0.000000


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.