The p.T1010I mutation, in the cytoplasmic juxtamembrane domain of MET has been shown to increase growth factor independent proliferation and motility in vitro in tumor cell lines in some studies. This mutation has seen more frequently in thyroid carcinomas than in the goiter controls. But its significance has been challenged by other studies which report a low incidence of T1010I mutation in both tumors and controls and not resulting in an enhanced c-MET phosphorylation. The utility of MET pathway inhibitors also continues to be explored. This variant has also been reported as a germline variant present in less than 1% of the general population. Its role in tumor development and progression continues to be studied. Due to conflicting reports of pathogenicity, this variant best characterized as a variant of uncertain significance (VUS) (https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/).
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