PKP2 variants in DCM cohorts


The table below lists the 7 rare (MAF<0.0001 in ExAC) protein-altering PKP2 variants identified in a cohort of 427 DCM patients (304 patients from OMGL, 123 patients from LMM). When this rare variant frequency of 0.01639 is compared with a background population rate of 0.01358, there is a case excess of 0.00281, although this is not statistically significant for protein-altering PKP2 variants in DCM (p=0.5287).


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 (427)OMGL classLMM class ExAC frequency
1. c.2447C>G p.T816Smissense 1VUS (1)0.000000
2. c.516C>A p.S172Rmissense 1VUS (1)0.000016
3. c.214G>T p.V72Lmissense 1VUS (1)0.000000
4. c.2623G>T p.A875Smissense 1VUS (1)0.000000
5. c.473G>A p.R158Kmissense 1VUS (1)0.000065
6. c.1889T>C p.I630Tmissense 1VUS (1)0.000016
7. c.462C>G p.S154Rmissense 1VUS (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.