The table below lists the 3 rare (MAF<0.0001 in ExAC) protein-altering ACTN2 variants identified in a cohort of 632 HCM patients. As the background population rate of rare protein-altering ACTN2 variants (0.01086) is greater than this case frequency (0.00475), there is no excess of variants in this HCM patient cohort, suggesting that protein-altering ACTN2 variants are not causative for HCM.
| No. | Variant (CDS)▼ | Variant (Protein) | Variant Type▼ | Cases (632)▼ | LMM class | ExAC frequency |
|---|---|---|---|---|---|---|
| 1. | c.1593G>A | p.W531X | nonsense | 1 | VUS favour pathogenic | 0.000000 |
| 2. | c.1057C>T | p.R353W | missense | 1 | VUS | 0.000016 |
| 3. | c.2386C>T | p.R796C | missense | 1 | VUS favour pathogenic | 0.000008 |
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.