PRKAG2 variants in HCM cohorts


The table below lists the 19 rare (MAF<0.0001 in ExAC) protein-altering PRKAG2 variants identified in a cohort of 1535 HCM patients. When this rare variant frequency of 0.01238 is compared with a background population rate of 0.00532, there is a statistically significant case excess of 0.00706 (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 (1535)OMGL class ExAC frequency
1. c.431C>T p.P144Lmissense 2VUS0.000024
2. c.905G>A p.R302Qmissense 2Pathogenic0.000000
3. c.1592G>A p.R531Qmissense 1Pathogenic0.000000
4. c.1647C>G p.D549Emissense 1VUS0.000000
5. c.989A>G p.Y330Cmissense 1VUS0.000000
6. c.1703C>T p.T568Mmissense 1VUS0.000098
7. c.1436T>C p.I479Tmissense 1VUS0.000000
8. c.1267C>A p.Q423Kmissense 1VUS0.000032
9. c.488C>T p.P163Lmissense 1VUS0.000000
10. c.1518A>C p.E506Dmissense 1VUS0.000000
11. c.1475T>A p.I492Nmissense 1VUS0.000032
12. c.608G>A p.R203Kmissense 1VUS0.000000
13. c.1648A>C p.I550Lmissense 1VUS0.000032
14. c.1066G>A p.E356Kmissense 1VUS0.000000
15. c.47G>C p.S16Tmissense 1VUS0.000000
16. c.1459T>G p.Y487Dmissense 1VUS0.000000
17. c.563A>G p.E188Gmissense 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.