TNNT2 variants in DCM cohorts


The table below lists the 11 rare (MAF<0.0001 in ExAC) protein-altering TNNT2 variants identified in a cohort of 498 DCM patients. When this rare variant frequency of 0.02209 is compared with a background population rate of 0.00242, there is a statistically significant case excess of 0.01967 (p<0.0001), which suggests that approximately 10 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 (498)OMGL class ExAC frequency
1. c.629_631delAGA inframe 7Pathogenic0.000000
2. c.421C>T p.R141Wmissense 1Pathogenic0.000000
3. c.613C>T p.R205Wmissense 1Likely Pathogenic0.000000
4. c.391C>T p.R131Wmissense 1Likely Pathogenic0.000008
5. c.476G>A p.R159Qmissense 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.