MYBPC3 variants in DCM cohorts


The table below lists the 20 rare (MAF<0.0001 in ExAC) protein-altering MYBPC3 variants identified in a cohort of 756 DCM patients. When this rare variant frequency of 0.02646 is compared with a background population rate of 0.01970, there is a case excess of 0.00676, 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 (756)LMM class ExAC frequency
1. c.529C>T p.R177Cmissense 2VUS0.000062
2. c.994G>A p.E332Kmissense 2VUS0.000009
3. c.3677G>T p.R1226Lmissense 1VUS0.000000
4. c.1422G>C p.E474Dmissense 1VUS0.000000
5. c.1373G>A p.R458Hmissense 1VUS0.000044
6. c.3005G>A p.R1002Qmissense 1VUS0.000046
7. c.917G>A p.R306Qmissense 1VUS0.000036
8. c.121C>T p.R41Cmissense 1VUS0.000034
9. c.148A>G p.S50Gmissense 1VUS0.000038
10. c.2641G>A p.V881Imissense 1VUS0.000018
11. c.713G>A p.R238Hmissense 1VUS0.000074
12. c.1976T>C p.I659Tmissense 1VUS favour pathogenic0.000000
13. c.206G>A p.R69Qmissense 1Likely Benign0.000024
14. c.2909G>A p.R970Qmissense 1VUS0.000032
15. c.1246G>A p.G416Smissense 1Likely Benign0.000028
16. c.166G>A p.G56Smissense 1VUS0.000015
17. c.745T>C p.C249Rmissense 1VUS0.000010
18. c.239delCinsGAGG inframe 1VUS favour pathogenic0.000000

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.