MYL3 variants in HCM cohorts


The table below lists the 23 rare (MAF<0.0001 in ExAC) protein-altering MYL3 variants identified in a cohort of 2650 HCM patients. When this rare variant frequency of 0.00868 is compared with a background population rate of 0.00182, there is a statistically significant case excess of 0.00686 (p<0.0001), which suggests that approximately 18 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.281G>A p.R94Hmissense 4Likely Pathogenic0.000000
2. c.427G>A p.E143Kmissense 3VUS0.000000
3. c.466G>A p.V156Mmissense 2VUS0.000016
4. c.461G>A p.R154Hmissense 2VUS favour pathogenic0.000024
5. c.460C>T p.R154Cmissense 2VUS favour pathogenic0.000016
6. c.517A>G p.M173Vmissense 2VUS favour pathogenic0.000000
7. c.170C>G p.A57Gmissense 2Likely Pathogenic0.000090
8. c.520G>C p.A174Pmissense 1VUS0.000000
9. c.11A>G p.K4Rmissense 1VUS0.000000
10. c.187C>T p.R63Cmissense 1VUS0.000008
11. c.446T>C p.M149Tmissense 1VUS0.000008
12. c.338C>T p.T113Imissense 1VUS0.000000
13. c.466G>T p.V156Lmissense 1VUS0.000000

References

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.