PKP2 truncating variants in ARVC cohorts

The table below lists the 95 rare (MAF<0.0001 in ExAC) truncating PKP2 variants identified in a cohort of 361 ARVC patients. When this rare variant frequency of 0.26316 is compared with a background population rate of 0.00076, there is a statistically significant case excess of 0.26240 (p<0.0001), which suggests that approximately 95 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.1999G>T p.E667Xnonsense 2Pathogenic0.000000
7. c.1748_1755dup p.Val587Thrfs*72frameshift 2Pathogenic0.000000
8. c.1237C>T p.R413Xnonsense 2Pathogenic0.000016
9. c.358G>T p.E120Xnonsense 2Pathogenic0.000000
10. c.1901del p.Asn634Thrfs*22frameshift 2Pathogenic0.000000
11. c.148_151delACAG p.Thr50SerfsX61frameshift 2Pathogenic0.000000
12. c.337-2A>T essential splice site 2Pathogenic0.000000
13. c.1063C>T p.R355Xnonsense 1Pathogenic0.000008
14. c.356dup p.Tyr119*frameshift 1Pathogenic0.000000
15. c.1171_1378del p.Val391Thrfs*6frameshift 1Likely Pathogenic0.000000
16. c.1170+1G>C essential splice site 1Pathogenic0.000000
17. c.1101dup p.Ser368Ilefs*19frameshift 1Pathogenic0.000000
18. c.2490-1G>C essential splice site 1Pathogenic0.000000
19. c.1211dup p.Val406Serfs*4frameshift 1Pathogenic0.000000
20. c.775G>T p.E259Xnonsense 1Pathogenic0.000000
21. c.2119C>T p.Q707Xnonsense 1Pathogenic0.000000
22. c.1968del p.Glu657Serfs*27frameshift 1Pathogenic0.000000
23. c.314del p.Pro105Leufs*7frameshift 1Pathogenic0.000000
24. c.253_256delGAGT frameshift 1Pathogenic0.000000
25. c.1372_1375del p.Ile458Glnfs*7frameshift 1Pathogenic0.000000
26. c.968_975delinsGCCTTT p.Gln323Argfs*12frameshift 1Pathogenic0.000000
27. c.1754C>G p.S585Xnonsense 1Pathogenic0.000000
28. c.1177C>T p.Q393Xnonsense 1Pathogenic0.000000
29. c.2058T>A p.Y686Xnonsense 1Pathogenic0.000000
30. c.1125_1132del p.Phe376Alafs*8frameshift 1Pathogenic0.000000
31. c.1892delinsTCC p.Tyr631Phefs*26frameshift 1Pathogenic0.000000
32. c.2509delA p.Ser837ValfsX94frameshift 1Pathogenic0.000000
33. c.2493T>A p.Y831Xnonsense 1Pathogenic0.000000
34. c.663C>A p.Y221Xnonsense 1Pathogenic0.000008
35. c.1689-1G>C essential splice site 1Pathogenic0.000008
36. c.1255_1279dup p.Asn427Ilefs*7frameshift 1Likely Pathogenic0.000000
37. c.1917_1935dup p.Gly646*frameshift 1Pathogenic0.000000
38. c.215del p.Val72Glyfs*40frameshift 1Pathogenic0.000000
39. c.235C>T p.R79Xnonsense 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.