PLN variants in HCM cohorts


The table below lists the 5 rare (MAF<0.0001 in ExAC) protein-altering PLN variants identified in a cohort of 1535 HCM patients. When this rare variant frequency of 0.00326 is compared with a background population rate of 0.00048, there is a statistically significant case excess of 0.00278 (p=0.0002), which suggests that approximately 4 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 (1535)OMGL class ExAC frequency
1. c.138dup p.Ile47Tyrfs*14frameshift 1VUS0.000000
2. c.63_64dup p.Gln22Leufs*19frameshift 1VUS0.000000
3. c.-97-2A>T essential splice site 1VUS0.000000
4. c.121T>A p.C41Smissense 1Likely Pathogenic0.000000
5. c.46T>C p.S16Pmissense 1VUS0.000000

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. 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.