TPM1 variants in DCM cohorts

The table below lists the 16 rare (MAF<0.0001 in ExAC) protein-altering TPM1 variants identified in a cohort of 756 DCM patients. When this rare variant frequency of 0.02116 is compared with a background population rate of 0.00086, there is a statistically significant case excess of 0.02030 (p<0.0001), which suggests that approximately 15 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 (756)▼	LMM class
1.	c.688G>A	p.D230N	missense	2	Pathogenic
2.	c.337C>G	p.L113V	missense	1	Likely Pathogenic
3.	c.97G>A	p.E33K	missense	1	VUS favour pathogenic
4.	c.2delT	p.Met1?	frameshift	1	VUS
5.	c.712C>T	p.R238W	missense	1	VUS favour pathogenic
6.	c.423G>C	p.M141I	missense	1	Likely Pathogenic
7.	c.632C>G	p.A211G	missense	1	Likely Pathogenic
8.	c.341A>G	p.E114G	missense	1	Likely Pathogenic
9.	c.23T>G	p.M8R	missense	1	Likely Pathogenic
10.	c.734C>T	p.S245L	missense	1	VUS
11.	c.118G>T	p.Glu40X	nonsense	1	VUS
12.	c.725C>T	p.A242V	missense	1	Likely Pathogenic
13.	c.416A>T	p.E139V	missense	1	Likely Pathogenic
14.	c.91G>A	p.A31T	missense	1	VUS
15.	c.275T>C	p.I92T	missense	1	Likely Pathogenic

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. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.