DSP variants in DCM cohorts


The table below lists the 32 rare (MAF<0.0001 in ExAC) protein-altering DSP variants identified in a cohort of 427 DCM patients (304 patients from OMGL, 123 patients from LMM). When this rare variant frequency of 0.07494 is compared with a background population rate of 0.03148, there is a statistically significant case excess of 0.04346 (p<0.0001), which suggests that approximately 19 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 (427)OMGL classLMM class ExAC frequency
1. c.943C>T p.R315Cmissense 2VUS (2)0.000074
2. c.939+1G>A essential splice site 2Pathogenic (1)Likely Pathogenic (1)0.000000
3. c.607G>A p.D203Nmissense 1VUS (1)0.000000
4. c.131G>A p.R44Qmissense 1VUS (1)0.000000
5. c.2848dupA frameshift 1Likely Pathogenic (1)0.000000
6. c.2900C>G p.S967Xnonsense 1Pathogenic (1)0.000000
7. c.478C>T p.R160Xnonsense 1Pathogenic (1)0.000000
8. c.8188del p.Gln2730Serfs*16frameshift 1VUS (1)0.000000
9. c.8481_8492del p.Ser2843_Arg2846delinframe 1VUS (1)0.000000
10. c.1381A>G p.I461Vmissense 1VUS (1)0.000000
11. c.4711C>T p.Q1571Xnonsense 1Pathogenic (1)0.000000
12. c.4022G>A p.R1341Hmissense 1VUS (1)0.000074
13. c.868G>A p.E290Kmissense 1VUS (1)0.000000
14. c.3751G>A p.D1251Nmissense 1VUS (1)0.000000
15. c.353T>A p.M118Kmissense 1VUS (1)0.000000
16. c.699G>A p.W233Xnonsense 1Likely Pathogenic (1)0.000000
17. c.3133C>T p.R1045Xnonsense 1Pathogenic (1)0.000000
18. c.521G>T p.C174Fmissense 1VUS (1)0.000057
19. c.7847C>T p.S2616Lmissense 1VUS (1)0.000008
20. c.1764_1766dup p.Glu589dupinframe 1Likely Pathogenic (1)0.000000
21. c.448C>T p.R150Xnonsense 1Pathogenic (1)0.000000
22. c.4670C>T p.T1557Mmissense 1VUS (1)0.000008
23. c.6788T>C p.I2263Tmissense 1VUS (1)0.000000
24. c.6885A>T p.Q2295Hmissense 1VUS (1)0.000000
25. c.1124dup p.Asn375Lysfs*9frameshift 1Pathogenic (1)0.000000
26. c.4221A>C p.E1407Dmissense 1VUS (1)0.000000
27. c.859A>G p.N287Dmissense 1VUS (1)0.000000
28. c.8495G>T p.G2832Vmissense 1VUS (1)0.000008
29. c.860A>G p.N287Smissense 1VUS (1)0.000008
30. c.3735_3741dup p.Asp1248Lysfs*7frameshift 1Pathogenic (1)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.

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.