ClinVar Miner

Submissions for variant NM_000245.4(MET):c.1125C>A (p.Asn375Lys)

dbSNP: rs776693512
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp 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.

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