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).
| No. | Variant (CDS)▼ | Variant (Protein) | Variant Type▼ | Cases (427)▼ | OMGL class | LMM class | ExAC frequency |
|---|---|---|---|---|---|---|---|
| 1. | c.214G>T | p.V72L | missense | 1 | VUS (1) | 0.000000 | |
| 2. | c.2623G>T | p.A875S | missense | 1 | VUS (1) | 0.000000 | |
| 3. | c.473G>A | p.R158K | missense | 1 | VUS (1) | 0.000065 | |
| 4. | c.462C>G | p.S154R | missense | 1 | VUS (1) | 0.000000 | |
| 5. | c.1889T>C | p.I630T | missense | 1 | VUS (1) | 0.000016 | |
| 6. | c.2447C>G | p.T816S | missense | 1 | VUS (1) | 0.000000 | |
| 7. | c.516C>A | p.S172R | missense | 1 | VUS (1) | 0.000016 |
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.