In silico analysis of TRPM4 variants of unknown clinical significance.

ABSTRACT:

Background

TRPM4 is a calcium-activated channel that selectively permeates monovalent cations. Genetic variants of the channel in cardiomyocytes are associated with various heart disorders, such as progressive familial heart block and Brugada syndrome. About97% of all known TRPM4 missense variants are classified as variants of unknown clinical significance (VUSs). The very large number of VUSs is a serious problem in diagnostics and treatment of inherited heart diseases.

Methods and results

We collected 233 benign or pathogenic missense variants in the superfamily of TRP channels from databases ClinVar, Humsavar and Ensembl Variation to compare performance of 22 algorithms that predict damaging variants. We found that ClinPred is the best-performing tool for TRP channels. We

SUBMITTER: Tarnovskaya SI 

PROVIDER: S-EPMC10723691 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature