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

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.