TPM1 non-truncating variants in DCM cohorts


The table below lists the 14 rare (MAF<0.0001 in ExAC) non-truncating TPM1 variants identified in a cohort of 756 DCM patients. When this rare variant frequency of 0.01852 is compared with a background population rate of 0.00084, there is a statistically significant case excess of 0.01768 (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 (756)LMM class ExAC frequency
1. c.688G>A p.D230Nmissense 2Pathogenic0.000000
2. c.341A>G p.E114Gmissense 1Likely Pathogenic0.000000
3. c.23T>G p.M8Rmissense 1Likely Pathogenic0.000000
4. c.91G>A p.A31Tmissense 1VUS0.000000
5. c.725C>T p.A242Vmissense 1Likely Pathogenic0.000000
6. c.712C>T p.R238Wmissense 1VUS favour pathogenic0.000000
7. c.416A>T p.E139Vmissense 1Likely Pathogenic0.000000
8. c.275T>C p.I92Tmissense 1Likely Pathogenic0.000000
9. c.337C>G p.L113Vmissense 1Likely Pathogenic0.000000
10. c.97G>A p.E33Kmissense 1VUS favour pathogenic0.000000
11. c.734C>T p.S245Lmissense 1VUS0.000000
12. c.423G>C p.M141Imissense 1Likely Pathogenic0.000000
13. c.632C>G p.A211Gmissense 1Likely Pathogenic0.000000

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.