ACTC1 variants in HCM cohorts


The table below lists the 13 rare (MAF<0.0001 in ExAC) protein-altering ACTC1 variants identified in a cohort of 2650 HCM patients. When this rare variant frequency of 0.00491 is compared with a background population rate of 0.00064, there is a statistically significant case excess of 0.00427 (p<0.0001), which suggests that approximately 11 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 (2650)LMM class ExAC frequency
1. c.301G>A p.E101Kmissense 4Pathogenic0.000008
2. c.793C>G p.Q265Emissense 2Likely Pathogenic0.000000
3. c.28C>A p.L10Mmissense 2VUS0.000025
4. c.229A>G p.I77Vmissense 1VUS0.000024
5. c.268C>T p.H90Ymissense 1VUS0.000008
6. c.850A>T p.I284Fmissense 1VUS0.000000
7. c.76G>A p.D26Nmissense 1VUS favour pathogenic0.000000
8. c.83C>T p.A28Vmissense 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.