TNNI3 non-truncating variants in DCM cohorts


The table below lists the 8 rare (MAF<0.0001 in ExAC) non-truncating TNNI3 variants identified in a cohort of 1239 DCM patients (483 patients from OMGL, 756 patients from LMM). When this rare variant frequency of 0.00646 is compared with a background population rate of 0.00186, there is a case excess of 0.00460, although this is not statistically significant for non-truncating TNNI3 variants in DCM (p=0.0033).


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 (1239)OMGL classLMM class ExAC frequency
1. c.65G>A p.R22Hmissense 1VUS (1)0.000000
2. c.356C>A p.T119Nmissense 2VUS (2)0.000033
3. c.470C>T p.A157Vmissense 1Likely Pathogenic (1)0.000000
4. c.488C>T p.A163Vmissense 1VUS (1)0.000000
5. c.544G>A p.E182Kmissense 1Likely Pathogenic (1)0.000000
6. c.550G>A p.E184Kmissense 1Likely Pathogenic (1)0.000000
7. c.557G>A p.R186Qmissense 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.