PLN variants in HCM cohorts

The table below lists the 7 rare (MAF<0.0001 in ExAC) protein-altering PLN variants identified in a cohort of 2167 HCM patients (1535 patients from OMGL, 632 patients from LMM). When this rare variant frequency of 0.00323 is compared with a background population rate of 0.00048, there is a statistically significant case excess of 0.00275 (p=0.0002), which suggests that approximately 6 of these variants may be pathogenic.

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 (2167)OMGL classLMM class ExAC frequency
1. c.116T>G p.L39Xnonsense 1Pathogenic (1)0.000008
2. c.121T>A p.C41Smissense 1Likely Pathogenic (1)0.000000
3. c.46T>C p.S16Pmissense 1VUS (1)0.000000
4. c.152T>C p.L51Pmissense 1VUS favour pathogenic (1)0.000000
5. c.138dup p.Ile47Tyrfs*14frameshift 1VUS (1)0.000000
6. c.63_64dup p.Gln22Leufs*19frameshift 1VUS (1)0.000000
7. c.-97-2A>T essential splice site 1VUS (1)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. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.