ACTN2 variants in DCM cohorts


The table below lists the 8 rare (MAF<0.0001 in ExAC) protein-altering ACTN2 variants identified in a cohort of 895 DCM patients (305 patients from OMGL, 590 patients from LMM). As the background population rate of rare protein-altering ACTN2 variants (0.01086) is greater than this case frequency (0.00894), there is no excess of variants in this DCM patient cohort, suggesting that protein-altering ACTN2 variants are not causative for DCM.


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 (895)OMGL classLMM class ExAC frequency
1. c.736A>G p.M246Vmissense 1VUS (1)0.000000
2. c.1384G>T p.A462Smissense 1VUS favour pathogenic (1)0.000016
3. c.2003C>G p.T668Rmissense 1VUS (1)0.000049
4. c.2289C>G p.N763Kmissense 1VUS (1)0.000000
5. c.556C>T p.L186Fmissense 1VUS (1)0.000082
6. c.1714C>T p.R572Wmissense 1VUS (1)0.000049
7. c.343G>A p.V115Mmissense 1VUS favour pathogenic (1)0.000000
8. c.130T>C p.F44Lmissense 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.