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.478C>T p.R160Xnonsense 1Pathogenic0.000000
3. c.3764G>A p.R1255Kmissense 1VUS0.000033
4. c.1325C>T p.S442Fmissense 1VUS0.000000
5. c.8309A>G p.Y2770Cmissense 1VUS0.000033
6. c.6118_6121del p.Ile2040Alafs*18frameshift 1Pathogenic0.000000
7. c.7940G>A p.G2647Dmissense 1VUS0.000008
8. c.2161G>A p.E721Kmissense 1Likely Pathogenic0.000000
9. c.1068dup p.Gln357Alafs*13frameshift 1Pathogenic0.000000
10. c.3562T>C p.Y1188Hmissense 1VUS0.000067
11. c.1124dup p.Asn375Lysfs*9frameshift 1Pathogenic0.000000
12. c.1759T>A p.Y587Nmissense 1VUS0.000000
13. c.2799G>C p.L933Fmissense 1VUS0.000075
14. c.818dup p.Asn274Glufs*15frameshift 1Pathogenic0.000000
15. c.4868C>G p.S1623Cmissense 1VUS0.000000
16. c.6496C>T p.R2166Xnonsense 1Pathogenic0.000000
17. c.4477G>T p.E1493Xnonsense 1Pathogenic0.000000
18. c.8077_8080del p.Lys2693Profs*3frameshift 1Likely Pathogenic0.000000
19. c.943C>T p.R315Cmissense 1VUS0.000074
20. c.4117A>G p.T1373Amissense 1VUS0.000091
21. c.1445G>A p.C482Ymissense 1VUS0.000000
22. c.2130+1G>C essential splice site 1Pathogenic0.000000
23. c.8390T>C p.I2797Tmissense 1VUS0.000032
24. c.1188_1195dup p.Ile399Argfs*44frameshift 1Pathogenic0.000000
25. c.6181C>T p.P2061Smissense 1VUS0.000000
26. c.3195C>G p.Y1065Xnonsense 1Likely Pathogenic0.000000
27. c.8120T>C p.M2707Tmissense 1VUS0.000008
28. c.3735_3741dup p.Asp1248Lysfs*7frameshift 1Pathogenic0.000000
29. c.2046C>A p.C682Xnonsense 1Likely Pathogenic0.000000
30. c.944G>C p.R315Pmissense 1VUS0.000000
31. c.5659_5660del p.Lys1887Glufs*2frameshift 1Pathogenic0.000000
32. c.7784C>T p.T2595Imissense 1VUS0.000008
33. c.4501G>T p.E1501Xnonsense 1Pathogenic0.000000
34. c.3133C>T p.R1045Xnonsense 1Pathogenic0.000000
35. c.1103T>C p.I368Tmissense 1VUS0.000074
36. c.415C>T p.Q139Xnonsense 1Pathogenic0.000000
37. c.4996C>T p.R1666Wmissense 1VUS0.000066
38. c.1755dup p.His586Thrfs*9frameshift 1Pathogenic0.000000
39. c.2609T>C p.I870Tmissense 1VUS0.000008
40. c.1352G>A p.R451Hmissense 1VUS0.000000
41. c.7012G>A p.G2338Rmissense 1VUS0.000000
42. c.3329del p.Lys1110Argfs*5frameshift 1Pathogenic0.000000

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.