TPM1 non-truncating variants in HCM cohorts

The table below lists the 44 rare (MAF<0.0001 in ExAC) non-truncating TPM1 variants identified in a cohort of 2912 HCM patients. When this rare variant frequency of 0.01511 is compared with a background population rate of 0.00084, there is a statistically significant case excess of 0.01427 (p<0.0001), which suggests that approximately 41 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 (2912)LMM class ExAC frequency
1. c.574G>A p.E192Kmissense 13Likely Pathogenic0.000000
2. c.523G>A p.D175Nmissense 4Pathogenic0.000000
3. c.644C>T p.S215Lmissense 3VUS favour pathogenic0.000008
4. c.829G>A p.A277Tmissense 2VUS favour benign0.000034
5. c.841A>G p.M281Vmissense 2VUS0.000026
6. c.64G>A p.A22Tmissense 2VUS favour pathogenic0.000000
7. c.82G>C p.D28Hmissense 2VUS favour pathogenic0.000000
8. c.762T>G p.D254Emissense 1Likely Pathogenic0.000000
9. c.548C>T p.A183Vmissense 1VUS0.000000
10. c.457C>G p.H153Dmissense 1Pathogenic0.000000
11. c.46G>C p.E16Qmissense 1Likely Pathogenic0.000000
12. c.343G>A p.E115Kmissense 1Likely Pathogenic0.000000
13. c.252C>G p.D84Emissense 1VUS0.000008
14. c.676A>C p.K226Qmissense 1VUS favour pathogenic0.000000
15. c.790A>G p.K264Emissense 1Likely Pathogenic0.000000
16. c.82G>A p.D28Nmissense 1VUS0.000000
17. c.842T>C p.M281Tmissense 1VUS0.000000
18. c.58G>A p.D20Nmissense 1VUS0.000000
19. c.835A>C p.N279Hmissense 1VUS favour pathogenic0.000000
20. c.559G>C p.E187Qmissense 1Likely Pathogenic0.000000
21. c.655G>A p.D219Nmissense 1Likely Pathogenic0.000000
22. c.850A>G p.I284Vmissense 1VUS0.000000
23. c.305C>A p.A102Dmissense 1VUS favour pathogenic0.000000


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