DSG2 variants in DCM cohorts


The table below lists the 3 rare (MAF<0.0001 in ExAC) protein-altering DSG2 variants identified in a cohort of 427 DCM patients (304 patients from OMGL, 123 patients from LMM). As the background population rate of rare protein-altering DSG2 variants (0.01298) is greater than this case frequency (0.00703), there is no excess of variants in this DCM patient cohort, suggesting that protein-altering DSG2 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 (427)OMGL classLMM class ExAC frequency
1. c.98A>G p.N33Smissense 1VUS (1)0.000016
2. c.3040G>A p.V1014Imissense 1VUS (1)0.000049
3. c.545A>G p.N182Smissense 1Likely Benign (1)0.000049

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.