PolyPhen-HCM is a method of predicting the effects of missense mutations in six genes associated with Hypertrophic Cardiomyopathy (HCM), described in Jordan, Kiezun, Baxter et al. 2011. It is currently available as a precomputed table of results for every possible variant in these six genes.
Download the precomputed table of results here:
This tool currently provides predictions for variants six genes: cardiac myosin binding protein C MYBPC3, slow cardiac myosin heavy chain MYH7, slow cardiac myosin regulatory light chain MYL2, cardiac troponin I TNNI3, cardiac troponin T TNNT2, and tropomyosin alpha-1 chain TPM1. Other genes that commonly contain HCM variants are not currently available, though we are looking into providing predictions for some of them.
When looking up your variants, be sure you use the numbering from the correct reference sequence:
|Gene Name||NCBI protein accession|
Every variant will give one of 3 results:
The current version (version 1.0) has the following statistics:
This prediction is designed to be used in combination with other methods, including family segregation data and population frequency. It is not recommended to use it as the sole source of information about any variant. In accordance with the recommendations of the IARC (Plon et al. 2008) and the ACMG (Richards et al. 2008).
Although this prediction has been validated against clinical data and undergone peer review, its effectiveness as a diagnostic has not been tested in any kind of controlled clinical trial. It requires interpretation by a qualified medical professional and integration with other sources of information before being used as a diagnostic.
Please cite the following paper when using this method:
Jordan D. M., Kiezun, A., Baxter, S. M., Agarwala, V., Green, R. C., Murray, M. F., Pugh, T., Lebo, M. S., Rehm, H. L., Funke, B. H., Sunyaev, S. R. Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy. Am. J. Hum. Genet. 88, 183-92 (2011)