The table below lists the 9 rare (MAF<0.0001 in ExAC) truncating DSP variants identified in a cohort of 304 DCM patients. When this rare variant frequency of 0.02961 is compared with a background population rate of 0.00070, there is a statistically significant case excess of 0.02891 (p<0.0001), which suggests that approximately 9 of these variants may be pathogenic.
| No. | Variant (CDS)▼ | Variant (Protein) | Variant Type▼ | Cases (304)▼ | OMGL class | ExAC frequency |
|---|---|---|---|---|---|---|
| 1. | c.939+1G>A | essential splice site | 1 | Pathogenic | 0.000000 | |
| 2. | c.4711C>T | p.Q1571X | nonsense | 1 | Pathogenic | 0.000000 |
| 3. | c.448C>T | p.R150X | nonsense | 1 | Pathogenic | 0.000000 |
| 4. | c.3133C>T | p.R1045X | nonsense | 1 | Pathogenic | 0.000000 |
| 5. | c.1124dup | p.Asn375Lysfs*9 | frameshift | 1 | Pathogenic | 0.000000 |
| 6. | c.8188del | p.Gln2730Serfs*16 | frameshift | 1 | VUS | 0.000000 |
| 7. | c.478C>T | p.R160X | nonsense | 1 | Pathogenic | 0.000000 |
| 8. | c.3735_3741dup | p.Asp1248Lysfs*7 | frameshift | 1 | Pathogenic | 0.000000 |
| 9. | c.2900C>G | p.S967X | nonsense | 1 | Pathogenic | 0.000000 |
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.