PKP2 variants in ARVC cohorts

The table below lists the 101 rare (MAF<0.0001 in ExAC) protein-altering PKP2 variants identified in a cohort of 361 ARVC patients. When this rare variant frequency of 0.27978 is compared with a background population rate of 0.01358, there is a statistically significant case excess of 0.26620 (p<0.0001), which suggests that approximately 96 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 (361)OMGL class ExAC frequency
1. c.2146-1G>C essential splice site 24Pathogenic0.000049
2. c.2197_2202delinsG p.His733Alafs*8frameshift 16Pathogenic0.000000
3. c.2489+1G>A essential splice site 8Pathogenic0.000024
4. c.275T>A p.L92Xnonsense 3Pathogenic0.000000
5. c.1132C>T p.Q378Xnonsense 3Pathogenic0.000000
6. c.1901del p.Asn634Thrfs*22frameshift 2Pathogenic0.000000
7. c.358G>T p.E120Xnonsense 2Pathogenic0.000000
8. c.1237C>T p.R413Xnonsense 2Pathogenic0.000016
9. c.337-2A>T essential splice site 2Pathogenic0.000000
10. c.148_151delACAG p.Thr50SerfsX61frameshift 2Pathogenic0.000000
11. c.1999G>T p.E667Xnonsense 2Pathogenic0.000000
12. c.1748_1755dup p.Val587Thrfs*72frameshift 2Pathogenic0.000000
13. c.2493T>A p.Y831Xnonsense 1Pathogenic0.000000
14. c.1211dup p.Val406Serfs*4frameshift 1Pathogenic0.000000
15. c.68G>A p.G23Emissense 1VUS0.000000
16. c.314del p.Pro105Leufs*7frameshift 1Pathogenic0.000000
17. c.2393C>G p.T798Rmissense 1VUS0.000000
18. c.1170+1G>C essential splice site 1Pathogenic0.000000
19. c.775G>T p.E259Xnonsense 1Pathogenic0.000000
20. c.235C>T p.R79Xnonsense 1Pathogenic0.000000
21. c.1968del p.Glu657Serfs*27frameshift 1Pathogenic0.000000
22. c.1372_1375del p.Ile458Glnfs*7frameshift 1Pathogenic0.000000
23. c.1754C>G p.S585Xnonsense 1Pathogenic0.000000
24. c.968_975delinsGCCTTT p.Gln323Argfs*12frameshift 1Pathogenic0.000000
25. c.2490-1G>C essential splice site 1Pathogenic0.000000
26. c.1063C>T p.R355Xnonsense 1Pathogenic0.000008
27. c.2062T>C p.S688Pmissense 1VUS0.000032
28. c.2058T>A p.Y686Xnonsense 1Pathogenic0.000000
29. c.1125_1132del p.Phe376Alafs*8frameshift 1Pathogenic0.000000
30. c.1892delinsTCC p.Tyr631Phefs*26frameshift 1Pathogenic0.000000
31. c.2540T>C p.L847Pmissense 1VUS0.000000
32. c.1255_1279dup p.Asn427Ilefs*7frameshift 1Likely Pathogenic0.000000
33. c.1917_1935dup p.Gly646*frameshift 1Pathogenic0.000000
34. c.215del p.Val72Glyfs*40frameshift 1Pathogenic0.000000
35. c.356dup p.Tyr119*frameshift 1Pathogenic0.000000
36. c.663C>A p.Y221Xnonsense 1Pathogenic0.000008
37. c.1177C>T p.Q393Xnonsense 1Pathogenic0.000000
38. c.253_256delGAGT frameshift 1Pathogenic0.000000
39. c.941G>A p.G314Emissense 1VUS0.000057
40. c.1171_1378del p.Val391Thrfs*6frameshift 1Likely Pathogenic0.000000
41. c.1101dup p.Ser368Ilefs*19frameshift 1Pathogenic0.000000
42. c.1689-1G>C essential splice site 1Pathogenic0.000008
43. c.2509delA p.Ser837ValfsX94frameshift 1Pathogenic0.000000
44. c.1114G>A p.A372Tmissense 1VUS0.000008
45. c.2119C>T p.Q707Xnonsense 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.