ACTN2 variants in HCM cohorts

The table below lists the 10 rare (MAF<0.0001 in ExAC) protein-altering ACTN2 variants identified in a cohort of 1439 HCM patients (807 patients from OMGL, 632 patients from LMM). As the background population rate of rare protein-altering ACTN2 variants (0.01086) is greater than this case frequency (0.00695), there is no excess of variants in this HCM patient cohort, suggesting that protein-altering ACTN2 variants are not causative for HCM.

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 (1439)▼	OMGL class	LMM class	ExAC frequency
1.	c.1593G>A	p.W531X	nonsense	1		VUS favour pathogenic (1)	0.000000
2.	c.690T>A	p.D230E	missense	1	VUS (1)		0.000098
3.	c.58A>G	p.M20V	missense	1	VUS (1)		0.000000
4.	c.1771A>G	p.I591V	missense	1	VUS (1)		0.000008
5.	c.1057C>T	p.R353W	missense	1		VUS (1)	0.000016
6.	c.979C>T	p.R327C	missense	1	VUS (1)		0.000024
7.	c.274A>G	p.M92V	missense	1	VUS (1)		0.000000
8.	c.2386C>T	p.R796C	missense	1		VUS favour pathogenic (1)	0.000008
9.	c.1714C>T	p.R572W	missense	1	VUS (1)		0.000049
10.	c.1958T>C	p.I653T	missense	1	VUS (1)		0.000000

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.