MYBPC3 variants in DCM cohorts


The table below lists the 29 rare (MAF<0.0001 in ExAC) protein-altering MYBPC3 variants identified in a cohort of 1161 DCM patients (405 patients from OMGL, 756 patients from LMM). When this rare variant frequency of 0.02498 is compared with a background population rate of 0.01970, there is a case excess of 0.00528, although this is not statistically significant for protein-altering MYBPC3 variants in DCM (p=0.2002).


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 (1161)OMGL classLMM class ExAC frequency
1. c.148A>G p.S50Gmissense 2VUS (1)VUS (1)0.000038
2. c.994G>A p.E332Kmissense 2VUS (2)0.000009
3. c.529C>T p.R177Cmissense 2VUS (2)0.000062
4. c.3677G>T p.R1226Lmissense 1VUS (1)0.000000
5. c.1123G>A p.V375Mmissense 1VUS (1)0.000009
6. c.1976T>C p.I659Tmissense 1VUS favour pathogenic (1)0.000000
7. c.3005G>A p.R1002Qmissense 1VUS (1)0.000046
8. c.745T>C p.C249Rmissense 1VUS (1)0.000010
9. c.2429G>A p.R810Hmissense 1VUS (1)0.000033
10. c.596T>G p.L199Rmissense 1VUS (1)0.000000
11. c.1246G>A p.G416Smissense 1Likely Benign (1)0.000028
12. c.3154A>G p.M1052Vmissense 1VUS (1)0.000033
13. c.1422G>C p.E474Dmissense 1VUS (1)0.000000
14. c.818G>A p.R273Hmissense 1VUS (1)0.000042
15. c.239delCinsGAGG inframe 1VUS favour pathogenic (1)0.000000
16. c.2641G>A p.V881Imissense 1VUS (1)0.000018
17. c.2300A>G p.K767Rmissense 1VUS (1)0.000016
18. c.917G>A p.R306Qmissense 1VUS (1)0.000036
19. c.1373G>A p.R458Hmissense 1VUS (1)0.000044
20. c.206G>A p.R69Qmissense 1Likely Benign (1)0.000024
21. c.713G>A p.R238Hmissense 1VUS (1)0.000074
22. c.2671C>T p.R891Wmissense 1VUS (1)0.000031
23. c.2909G>A p.R970Qmissense 1VUS (1)0.000032
24. c.1724G>T p.G575Vmissense 1VUS (1)0.000000
25. c.166G>A p.G56Smissense 1VUS (1)0.000015
26. c.121C>T p.R41Cmissense 1VUS (1)0.000034

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.