LMNA non-truncating variants in DCM cohorts


The table below lists the 30 rare (MAF<0.0001 in ExAC) non-truncating LMNA variants identified in a cohort of 1044 DCM patients (304 patients from OMGL, 740 patients from LMM). When this rare variant frequency of 0.02874 is compared with a background population rate of 0.00608, there is a statistically significant case excess of 0.02266 (p<0.0001), which suggests that approximately 24 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 (1044)OMGL classLMM class ExAC frequency
1. c.1003C>T p.R335Wmissense 3Likely Pathogenic (3)0.000000
2. c.481G>A p.E161Kmissense 2Pathogenic (2)0.000000
3. c.868G>A p.E290Kmissense 2VUS (1)VUS favour pathogenic (1)0.000000
4. c.1621C>T p.R541Cmissense 2Likely Pathogenic (2)0.000000
5. c.356G>C p.R119Pmissense 1Likely Pathogenic (1)0.000000
6. c.266G>A p.R89Hmissense 1VUS (1)0.000000
7. c.949G>A p.E317Kmissense 1Likely Pathogenic (1)0.000000
8. c.1046G>A p.R349Qmissense 1VUS (1)0.000000
9. c.1442A>G p.Y481Cmissense 1Likely Pathogenic (1)0.000000
10. c.863C>G p.A288Gmissense 1Likely Pathogenic (1)0.000000
11. c.1622G>A p.R541Hmissense 1Likely Pathogenic (1)0.000093
12. c.1111_1125del p.Met371_Ala375delinframe 1Likely Pathogenic (1)0.000000
13. c.1106T>C p.L369Pmissense 1Likely Pathogenic (1)0.000000
14. c.436G>A p.A146Tmissense 1VUS favour pathogenic (1)0.000000
15. c.1412G>A p.R471Hmissense 1Likely Pathogenic (1)0.000000
16. c.350A>G p.K117Rmissense 1VUS (1)0.000068
17. c.992G>A p.R331Qmissense 1Likely Pathogenic (1)0.000016
18. c.154C>G p.L52Vmissense 1Likely Pathogenic (1)0.000000
19. c.976T>A p.S326Tmissense 1Likely Pathogenic (1)0.000059
20. c.799T>C p.Y267Hmissense 1Pathogenic (1)0.000000
21. c.175C>A p.L59Mmissense 1VUS (1)0.000000
22. c.739G>A p.E247Kmissense 1VUS (1)0.000000
23. c.1129C>T p.R377Cmissense 1Likely Pathogenic (1)0.000000
24. c.448A>C p.T150Pmissense 1Likely Pathogenic (1)0.000000
25. c.1201C>T p.R401Cmissense 1VUS (1)0.000033

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.