rs1554757211

Description

The I764T variant in the MUSK gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I764T variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I764T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs within the protein kinase domain, at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The I764T variant is a strong candidate for a pathogenic variant.However the possibility that I764T may be a rare benign variant cannot be excluded.

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].