The variant mechanism is the functional route by which a pathogenic variant causes disease, as distinct from which gene is affected. In Charcot-Marie-Tooth disease (CMT), the gene identifies the cause, but the mechanism explains how the variant does harm: by reducing the protein’s normal activity (loss of function), by producing a mutant protein that interferes with its normal counterpart (dominant-negative), or by adding a new toxic activity or an excess of normal activity (toxic gain of function). A single subtype can act through more than one route.
Each CMT subtype’s mechanism call is presented in the CMT Variant Mechanisms Browser.
