RBM20 variants in DCM cohorts


The table below lists the 9 rare (MAF<0.0001 in ExAC) protein-altering RBM20 variants identified in a cohort of 156 DCM patients. When this rare variant frequency of 0.05769 is compared with a background population rate of 0.01414, there is a statistically significant case excess of 0.04355 (p=0.0005), which suggests that approximately 7 of these variants may be pathogenic.


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



No. Variant (CDS) Variant (Protein) Variant Type Cases (156)LMM class ExAC frequency
1. c.3022C>T p.R1008Wmissense 1VUS (1)0.000045
2. c.2017C>T p.R673Wmissense 1VUS favour pathogenic (1)0.000053
3. c.2728A>C p.T910Pmissense 1VUS (1)0.000000
4. c.1459G>A p.V487Mmissense 1VUS (1)0.000050
5. c.1913C>T p.P638Lmissense 1Pathogenic (1)0.000000
6. c.2108G>A p.R703Kmissense 1VUS favour pathogenic (1)0.000000
7. c.2737G>A p.E913Kmissense 1VUS (1)0.000000
8. c.1633G>A p.V545Imissense 1Likely Benign (1)0.000045
9. c.1907G>A p.R636Hmissense 1VUS favour 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.