VCL variants in DCM cohorts


The table below lists the 13 rare (MAF<0.0001 in ExAC) protein-altering VCL variants identified in a cohort of 590 DCM patients. When this rare variant frequency of 0.02203 is compared with a background population rate of 0.01016, there is a case excess of 0.01187, although this is not statistically significant for protein-altering VCL variants in DCM (p=0.0111).


Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      LMM



No. Variant (CDS) Variant (Protein) Variant Type Cases (590)LMM class ExAC frequency
1. c.1639C>T p.R547Xnonsense 1Likely Pathogenic (1)0.000008
2. c.3092G>A p.R1031Qmissense 1VUS (1)0.000000
3. c.952C>T p.R318Cmissense 1VUS (1)0.000024
4. c.2862_2864delGTT inframe 1VUS favour pathogenic (1)0.000000
5. c.3226C>T p.R1076Wmissense 1VUS (1)0.000015
6. c.659dupA frameshift 1Likely Pathogenic (1)0.000000
7. c.2852C>G p.P951Rmissense 1Likely Benign (1)0.000008
8. c.313C>T p.R105Xnonsense 1Likely Pathogenic (1)0.000008
9. c.1844C>T p.A615Vmissense 1VUS (1)0.000024
10. c.1390A>C p.K464Qmissense 1VUS (1)0.000000
11. c.3373C>T p.R1125Cmissense 1VUS (1)0.000024
12. c.2444A>G p.K815Rmissense 1VUS favour pathogenic (1)0.000016
13. c.562C>T p.R188Xnonsense 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.