TPM1 non-truncating variants in DCM cohorts


The table below lists the 19 rare (MAF<0.0001 in ExAC) non-truncating TPM1 variants identified in a cohort of 1111 DCM patients (355 patients from OMGL, 756 patients from LMM). When this rare variant frequency of 0.01710 is compared with a background population rate of 0.00084, there is a statistically significant case excess of 0.01626 (p<0.0001), which suggests that approximately 18 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 (1111)OMGL classLMM class ExAC frequency
1. c.688G>A p.D230Nmissense 3Pathogenic (1)Pathogenic (2)0.000000
2. c.337C>G p.L113Vmissense 2Likely Pathogenic (1)Likely Pathogenic (1)0.000000
3. c.97G>A p.E33Kmissense 1VUS favour pathogenic (1)0.000000
4. c.91G>A p.A31Tmissense 1VUS (1)0.000000
5. c.712C>T p.R238Wmissense 1VUS favour pathogenic (1)0.000000
6. c.423G>C p.M141Imissense 1Likely Pathogenic (1)0.000000
7. c.695T>G p.L232Rmissense 1VUS (1)0.000000
8. c.632C>G p.A211Gmissense 1Likely Pathogenic (1)0.000000
9. c.341A>G p.E114Gmissense 1Likely Pathogenic (1)0.000000
10. c.359C>T p.A120Vmissense 1VUS (1)0.000000
11. c.23T>G p.M8Rmissense 1Likely Pathogenic (1)0.000000
12. c.734C>T p.S245Lmissense 1VUS (1)0.000000
13. c.725C>T p.A242Vmissense 1Likely Pathogenic (1)0.000000
14. c.416A>T p.E139Vmissense 1Likely Pathogenic (1)0.000000
15. c.368G>C p.S123Tmissense 1VUS (1)0.000000
16. c.275T>C p.I92Tmissense 1Likely Pathogenic (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.