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.148_151delACAG p.Thr50SerfsX61frameshift 2Pathogenic0.000000
7. c.1901del p.Asn634Thrfs*22frameshift 2Pathogenic0.000000
8. c.358G>T p.E120Xnonsense 2Pathogenic0.000000
9. c.1237C>T p.R413Xnonsense 2Pathogenic0.000016
10. c.1999G>T p.E667Xnonsense 2Pathogenic0.000000
11. c.337-2A>T essential splice site 2Pathogenic0.000000
12. c.1748_1755dup p.Val587Thrfs*72frameshift 2Pathogenic0.000000
13. c.1689-1G>C essential splice site 1Pathogenic0.000008
14. c.1101dup p.Ser368Ilefs*19frameshift 1Pathogenic0.000000
15. c.941G>A p.G314Emissense 1VUS0.000057
16. c.1211dup p.Val406Serfs*4frameshift 1Pathogenic0.000000
17. c.253_256delGAGT frameshift 1Pathogenic0.000000
18. c.2119C>T p.Q707Xnonsense 1Pathogenic0.000000
19. c.1114G>A p.A372Tmissense 1VUS0.000008
20. c.68G>A p.G23Emissense 1VUS0.000000
21. c.1968del p.Glu657Serfs*27frameshift 1Pathogenic0.000000
22. c.2393C>G p.T798Rmissense 1VUS0.000000
23. c.1372_1375del p.Ile458Glnfs*7frameshift 1Pathogenic0.000000
24. c.314del p.Pro105Leufs*7frameshift 1Pathogenic0.000000
25. c.2058T>A p.Y686Xnonsense 1Pathogenic0.000000
26. c.1170+1G>C essential splice site 1Pathogenic0.000000
27. c.1754C>G p.S585Xnonsense 1Pathogenic0.000000
28. c.2490-1G>C essential splice site 1Pathogenic0.000000
29. c.2493T>A p.Y831Xnonsense 1Pathogenic0.000000
30. c.968_975delinsGCCTTT p.Gln323Argfs*12frameshift 1Pathogenic0.000000
31. c.2540T>C p.L847Pmissense 1VUS0.000000
32. c.1892delinsTCC p.Tyr631Phefs*26frameshift 1Pathogenic0.000000
33. c.775G>T p.E259Xnonsense 1Pathogenic0.000000
34. c.1125_1132del p.Phe376Alafs*8frameshift 1Pathogenic0.000000
35. c.235C>T p.R79Xnonsense 1Pathogenic0.000000
36. c.2062T>C p.S688Pmissense 1VUS0.000032
37. c.1917_1935dup p.Gly646*frameshift 1Pathogenic0.000000
38. c.1063C>T p.R355Xnonsense 1Pathogenic0.000008
39. c.1255_1279dup p.Asn427Ilefs*7frameshift 1Likely Pathogenic0.000000
40. c.215del p.Val72Glyfs*40frameshift 1Pathogenic0.000000
41. c.1171_1378del p.Val391Thrfs*6frameshift 1Likely Pathogenic0.000000
42. c.1177C>T p.Q393Xnonsense 1Pathogenic0.000000
43. c.356dup p.Tyr119*frameshift 1Pathogenic0.000000
44. c.663C>A p.Y221Xnonsense 1Pathogenic0.000008
45. c.2509delA p.Ser837ValfsX94frameshift 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.