ACTC1 variants in HCM cohorts


The table below lists the 9 rare (MAF<0.0001 in ExAC) protein-altering ACTC1 variants identified in a cohort of 1535 HCM patients. When this rare variant frequency of 0.00586 is compared with a background population rate of 0.00064, there is a statistically significant case excess of 0.00522 (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.1069A>G p.M357Vmissense 1VUS0.000000
2. c.301G>A p.E101Kmissense 1Pathogenic0.000008
3. c.124C>T p.H42Ymissense 1VUS0.000000
4. c.1099G>A p.A367Tmissense 1VUS0.000000
5. c.797C>T p.P266Lmissense 1VUS0.000000
6. c.76G>A p.D26Nmissense 1VUS0.000000
7. c.110T>C p.V37Amissense 1VUS0.000000
8. c.850A>T p.I284Fmissense 1VUS0.000000
9. c.752C>G p.T251Smissense 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.