DSG2 variants in ARVC cohorts

The table below lists the 17 rare (MAF<0.0001 in ExAC) protein-altering DSG2 variants identified in a cohort of 354 ARVC patients. When this rare variant frequency of 0.04802 is compared with a background population rate of 0.01298, there is a statistically significant case excess of 0.03504 (p<0.0001), which suggests that approximately 12 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 (354)OMGL class ExAC frequency
1. c.2434G>A p.G812Smissense 2Likely Pathogenic0.000016
2. c.1038_1040delGAA p.Lys346delinframe 2Likely Pathogenic0.000000
3. c.136C>T p.R46Wmissense 1Likely Pathogenic0.000008
4. c.3342G>T p.Q1114Hmissense 1VUS0.000000
5. c.1880-2A>G essential splice site 1Pathogenic0.000000
6. c.1765_1766insAA p.Thr589Lysfs*31frameshift 1Likely Pathogenic0.000000
7. c.523+1G>A essential splice site 1Likely Pathogenic0.000000
8. c.874C>T p.R292Cmissense 1VUS0.000033
9. c.178G>A p.E60Kmissense 1VUS0.000000
10. c.145C>T p.R49Cmissense 1Likely Pathogenic0.000016
11. c.2332G>T p.D778Ymissense 1VUS0.000000
12. c.852_855del p.Asn284Lysfs*4frameshift 1Likely Pathogenic0.000000
13. c.908C>T p.S303Fmissense 1VUS0.000008
14. c.495dup p.Gly166Trpfs*4frameshift 1Pathogenic0.000000
15. c.146G>A p.R49Hmissense 1Likely Pathogenic0.000008


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.