MYL2 non-truncating variants in HCM cohorts


The table below lists the 10 rare (MAF<0.0001 in ExAC) non-truncating MYL2 variants identified in a cohort of 1535 HCM patients. When this rare variant frequency of 0.00651 is compared with a background population rate of 0.00154, there is a statistically significant case excess of 0.00497 (p<0.0001), which suggests that approximately 8 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.64G>A p.E22Kmissense 3Pathogenic0.000008
2. c.173G>A p.R58Qmissense 2Pathogenic0.000008
3. c.257T>C p.F86Smissense 2VUS0.000008
4. c.80A>G p.Q27Rmissense 1VUS0.000000
5. c.458A>G p.K153Rmissense 1VUS0.000000
6. c.485_487del p.Gly162delinframe 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.