DSP variants in DCM cohorts


The table below lists the 23 rare (MAF<0.0001 in ExAC) protein-altering DSP variants identified in a cohort of 304 DCM patients. When this rare variant frequency of 0.07566 is compared with a background population rate of 0.03148, there is a statistically significant case excess of 0.04418 (p<0.0001), which suggests that approximately 13 of these variants may be pathogenic.


Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM



No. Variant (CDS) Variant (Protein) Variant Type Cases (304)OMGL class ExAC frequency
1. c.478C>T p.R160Xnonsense 1Pathogenic0.000000
2. c.353T>A p.M118Kmissense 1VUS0.000000
3. c.3133C>T p.R1045Xnonsense 1Pathogenic0.000000
4. c.1764_1766dup p.Glu589dupinframe 1Likely Pathogenic0.000000
5. c.6788T>C p.I2263Tmissense 1VUS0.000000
6. c.939+1G>A essential splice site 1Pathogenic0.000000
7. c.7847C>T p.S2616Lmissense 1VUS0.000008
8. c.4221A>C p.E1407Dmissense 1VUS0.000000
9. c.1124dup p.Asn375Lysfs*9frameshift 1Pathogenic0.000000
10. c.521G>T p.C174Fmissense 1VUS0.000057
11. c.4022G>A p.R1341Hmissense 1VUS0.000074
12. c.859A>G p.N287Dmissense 1VUS0.000000
13. c.3735_3741dup p.Asp1248Lysfs*7frameshift 1Pathogenic0.000000
14. c.8188del p.Gln2730Serfs*16frameshift 1VUS0.000000
15. c.448C>T p.R150Xnonsense 1Pathogenic0.000000
16. c.2900C>G p.S967Xnonsense 1Pathogenic0.000000
17. c.131G>A p.R44Qmissense 1VUS0.000000
18. c.4711C>T p.Q1571Xnonsense 1Pathogenic0.000000
19. c.1381A>G p.I461Vmissense 1VUS0.000000
20. c.860A>G p.N287Smissense 1VUS0.000008
21. c.4670C>T p.T1557Mmissense 1VUS0.000008
22. c.3751G>A p.D1251Nmissense 1VUS0.000000
23. c.868G>A p.E290Kmissense 1VUS0.000000

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.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.