CSRP3 variants in DCM cohorts


The table below lists the 4 rare (MAF<0.0001 in ExAC) protein-altering CSRP3 variants identified in a cohort of 945 DCM patients (355 patients from OMGL, 590 patients from LMM). When this rare variant frequency of 0.00423 is compared with a background population rate of 0.00324, there is a case excess of 0.00099, although this is not statistically significant for protein-altering CSRP3 variants in DCM (p=0.5559).


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 (945)OMGL classLMM class ExAC frequency
1. c.136A>C p.S46Rmissense 1Likely Pathogenic (1)0.000033
2. c.148G>A p.A50Tmissense 1VUS (1)0.000041
3. c.509-3_509-2delCA essential splice site 1VUS (1)0.000024
4. c.535A>G p.T179Amissense 1VUS (1)0.000016

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.