MYH7 variants in DCM cohorts


The table below lists the 25 rare (MAF<0.0001 in ExAC) protein-altering MYH7 variants identified in a cohort of 559 DCM patients. When this rare variant frequency of 0.04472 is compared with a background population rate of 0.01398, there is a statistically significant case excess of 0.03074 (p<0.0001), which suggests that approximately 17 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 (559)OMGL class ExAC frequency
1. c.5530G>A p.E1844Kmissense 2VUS0.000008
2. c.4300C>T p.R1434Cmissense 2Likely Pathogenic0.000000
3. c.532G>A p.G178Rmissense 2Likely Pathogenic0.000000
4. c.431G>T p.G144Vmissense 2Likely Pathogenic0.000000
5. c.4004C>T p.S1335Lmissense 1VUS0.000033
6. c.2015G>T p.C672Fmissense 1Likely Pathogenic0.000000
7. c.4643A>T p.E1548Vmissense 1VUS0.000000
8. c.2455C>T p.R819Wmissense 1VUS0.000000
9. c.728G>A p.R243Hmissense 1Likely Pathogenic0.000008
10. c.3284A>G p.E1095Gmissense 1VUS0.000000
11. c.5329G>A p.A1777Tmissense 1VUS0.000041
12. c.2456G>A p.R819Qmissense 1VUS0.000008
13. c.589G>A p.V197Imissense 1VUS0.000016
14. c.4638G>T p.E1546Dmissense 1VUS0.000000
15. c.4048G>A p.E1350Kmissense 1VUS0.000000
16. c.5020G>T p.V1674Lmissense 1VUS0.000000
17. c.2441T>G p.I814Smissense 1VUS0.000000
18. c.2682A>C p.E894Dmissense 1VUS0.000000
19. c.1045A>G p.M349Vmissense 1VUS0.000024
20. c.541G>A p.G181Rmissense 1Likely Pathogenic0.000008
21. c.3464G>A p.G1155Emissense 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. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.