DES variants in DCM cohorts


The table below lists the 5 rare (MAF<0.0001 in ExAC) protein-altering DES variants identified in a cohort of 590 DCM patients. When this rare variant frequency of 0.00847 is compared with a background population rate of 0.00472, there is a case excess of 0.00375, although this is not statistically significant for protein-altering DES variants in DCM (p=0.0806).


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 (590)LMM class ExAC frequency
1. c.38C>T p.S13Fmissense 1Pathogenic0.000000
2. c.600delG frameshift 1Likely Pathogenic0.000000
3. c.193G>A p.G65Smissense 1VUS0.000056
4. c.127A>G p.K43Emissense 1VUS0.000000
5. c.735+3A>G p.Asp214_Glu245delinframe 1Pathogenic0.000000
6. c.1285C>T p.R429Xnonsense 1Likely Pathogenic0.000016

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.