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


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.