MYBPC3 non-truncating variants in DCM cohorts


The table below lists the 29 rare (MAF<0.0001 in ExAC) non-truncating 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 0.01884, there is a case excess of 0.00614, although this is not statistically significant for non-truncating MYBPC3 variants in DCM (p=0.1278).


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

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.