DSP variants in ARVC cohorts

The table below lists the 43 rare (MAF<0.0001 in ExAC) protein-altering DSP variants identified in a cohort of 352 ARVC patients. When this rare variant frequency of 0.12216 is compared with a background population rate of 0.03148, there is a statistically significant case excess of 0.09068 (p<0.0001), which suggests that approximately 32 of these variants may be pathogenic.

Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      OMGL

No. Variant (CDS) Variant (Protein) Variant Type Cases (352)OMGL class ExAC frequency
1. c.1288G>T p.E430Xnonsense 2Pathogenic0.000000
2. c.3562T>C p.Y1188Hmissense 1VUS0.000067
3. c.1124dup p.Asn375Lysfs*9frameshift 1Pathogenic0.000000
4. c.818dup p.Asn274Glufs*15frameshift 1Pathogenic0.000000
5. c.4868C>G p.S1623Cmissense 1VUS0.000000
6. c.6496C>T p.R2166Xnonsense 1Pathogenic0.000000
7. c.1759T>A p.Y587Nmissense 1VUS0.000000
8. c.2799G>C p.L933Fmissense 1VUS0.000075
9. c.4477G>T p.E1493Xnonsense 1Pathogenic0.000000
10. c.8077_8080del p.Lys2693Profs*3frameshift 1Likely Pathogenic0.000000
11. c.943C>T p.R315Cmissense 1VUS0.000074
12. c.4117A>G p.T1373Amissense 1VUS0.000091
13. c.1445G>A p.C482Ymissense 1VUS0.000000
14. c.2130+1G>C essential splice site 1Pathogenic0.000000
15. c.8390T>C p.I2797Tmissense 1VUS0.000032
16. c.6181C>T p.P2061Smissense 1VUS0.000000
17. c.3195C>G p.Y1065Xnonsense 1Likely Pathogenic0.000000
18. c.1188_1195dup p.Ile399Argfs*44frameshift 1Pathogenic0.000000
19. c.8120T>C p.M2707Tmissense 1VUS0.000008
20. c.3735_3741dup p.Asp1248Lysfs*7frameshift 1Pathogenic0.000000
21. c.2046C>A p.C682Xnonsense 1Likely Pathogenic0.000000
22. c.944G>C p.R315Pmissense 1VUS0.000000
23. c.5659_5660del p.Lys1887Glufs*2frameshift 1Pathogenic0.000000
24. c.7784C>T p.T2595Imissense 1VUS0.000008
25. c.4501G>T p.E1501Xnonsense 1Pathogenic0.000000
26. c.3133C>T p.R1045Xnonsense 1Pathogenic0.000000
27. c.1103T>C p.I368Tmissense 1VUS0.000074
28. c.4996C>T p.R1666Wmissense 1VUS0.000066
29. c.1755dup p.His586Thrfs*9frameshift 1Pathogenic0.000000
30. c.2609T>C p.I870Tmissense 1VUS0.000008
31. c.415C>T p.Q139Xnonsense 1Pathogenic0.000000
32. c.1352G>A p.R451Hmissense 1VUS0.000000
33. c.7012G>A p.G2338Rmissense 1VUS0.000000
34. c.3329del p.Lys1110Argfs*5frameshift 1Pathogenic0.000000
35. c.478C>T p.R160Xnonsense 1Pathogenic0.000000
36. c.1325C>T p.S442Fmissense 1VUS0.000000
37. c.8309A>G p.Y2770Cmissense 1VUS0.000033
38. c.3764G>A p.R1255Kmissense 1VUS0.000033
39. c.7940G>A p.G2647Dmissense 1VUS0.000008
40. c.2161G>A p.E721Kmissense 1Likely Pathogenic0.000000
41. c.1068dup p.Gln357Alafs*13frameshift 1Pathogenic0.000000
42. c.6118_6121del p.Ile2040Alafs*18frameshift 1Pathogenic0.000000


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.