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.1038_1040delGAA	p.Lys346del	inframe	2	Likely Pathogenic	0.000000
2.	c.2434G>A	p.G812S	missense	2	Likely Pathogenic	0.000016
3.	c.136C>T	p.R46W	missense	1	Likely Pathogenic	0.000008
4.	c.523+1G>A		essential splice site	1	Likely Pathogenic	0.000000
5.	c.178G>A	p.E60K	missense	1	VUS	0.000000
6.	c.874C>T	p.R292C	missense	1	VUS	0.000033
7.	c.2332G>T	p.D778Y	missense	1	VUS	0.000000
8.	c.145C>T	p.R49C	missense	1	Likely Pathogenic	0.000016
9.	c.852_855del	p.Asn284Lysfs*4	frameshift	1	Likely Pathogenic	0.000000
10.	c.495dup	p.Gly166Trpfs*4	frameshift	1	Pathogenic	0.000000
11.	c.908C>T	p.S303F	missense	1	VUS	0.000008
12.	c.3342G>T	p.Q1114H	missense	1	VUS	0.000000
13.	c.146G>A	p.R49H	missense	1	Likely Pathogenic	0.000008
14.	c.1765_1766insAA	p.Thr589Lysfs*31	frameshift	1	Likely Pathogenic	0.000000
15.	c.1880-2A>G		essential splice site	1	Pathogenic	0.000000

References

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.