Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002233262 | SCV000822475 | uncertain significance | Renal cell carcinoma | 2018-05-14 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with lysine at codon 375 of the MET protein (p.Asn375Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs776693512, ExAC 0.007%). This variant has been observed in a family affected with lung cancer (PMID: 28294470). Experimental studies have shown that this missense change results in a protein with decreased agonist binding and tumor promoting capabilities, inconsistent with the typical gain-of-function variants associated with MET-related disease (PMID: 28294470). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |