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