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Interpretation 224
Tier 3
MET
Variants
MET T1010I
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Follicular Carcinoma
Interpretation

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/).

Citations
  1. Wasenius VM, et al. MET receptor tyrosine kinase sequence alterations in differentiated thyroid carcinoma. Am J Surg Pathol 2005;29(4):544-9
  2. Zenali M, et al. Retrospective Review of MET Gene Mutations. Oncoscience 2015;2(5):533-41
  3. https://www.ncbi.nlm.nih.gov/clinvar/variation/41624/
Last updated: 2018-03-06 17:56:37 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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