Gene Variant Detail

Gene MET
Variant Y1230H
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions MET Y1230H lies within the protein kinase domain of the Met protein (UniProt.org). Y1230H results in constitutive Met autophosphorylation and increased substrate phosphorylation, and is transforming in cell culture (PMID: 9826708), and has been associated with acquired resistance to Xalkori (crizotinib) (PMID: 28522754).
Associated Drug Resistance Y

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Transcript NM_000245
gDNA chr7:g.116783359T>C
cDNA c.3688T>C
Protein p.Y1230H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_000245 chr7:g.116783359T>C c.3688T>C p.Y1230H RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET over exp MET Y1230H stomach cancer resistant PHA-665752 Preclinical - Cell line xenograft Actionable In a preclinical study, MET Y1230H was associated with resistance to PHA-665752 in a gastric cancer cell line with MET over expression in culture (PMID: 21266357). 21266357
MET F1200L MET Y1230H stomach cancer sensitive Glesatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L was sensitive to treatment with Glesatinib (MGCD265), demonstrating cell growth inhibition in culture (PMID: 28765324). 28765324 15494073
MET F1200L MET Y1230H stomach cancer resistant Capmatinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) co-harboring MET Y1230H and MET F1200L demonstrated resistance when treated with Capmatinib (INC280) in culture (PMID: 28765324). 28765324 15494073
MET F1200L MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a gastric adenocarcinoma cell line (PMID: 15494073) treated with Xalkori (crizotinib) in culture for several months developed resistance and was found to co-harbor MET Y1230H and MET F1200L(PMID: 28765324). 28765324 15494073
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring MET deletion exon 14 and MET amplification demonstrated resistance to Xalkori (crizotinib), and the patient was found to have acquired MET Y1230H, MET D1228N, MET Y1230S, and MET G1163R (PMID: 28765324). 28765324
MET amp MET del exon14 MET D1228N MET G1163R MET Y1230H MET Y1230S lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring MET deletion exon 14 responded to Xalkori (crizotinib), demonstrating a near complete response at 3 months, however, after 9 months progression ensued and a re-biospy identified MET del exon14, MET amplification, MET D1228N, MET Y1230H, MET Y1230S, and MET G1163R (PMID: 28522754). 28522754
MET over exp MET Y1230C MET Y1230H stomach cancer resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, acquired MET Y1230C and MET Y1230H mutations were associated with secondary resistance to Xalkori (crizotinib) in a MET-over expressing gastric cancer cell line xenograft model, and cells derived from this model demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21266357). 21266357
MET Y1230H Advanced Solid Tumor predicted - resistant Capmatinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Capmatinib (INC280), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive BMS-777607 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to Y1230H in humans) were sensitive to treatment with BMS-777607 (ASLAN002), demonstrating inhibition of cell growth in culture (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive Cabozantinib Preclinical Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were sensitive to treatment with Cometriq (Cabometyx, cabozantinib), demonstrating inhibition of cell growth in culture and tumor growth inhibition in mouse models (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Xalkori (crizotinib), demonstrating sustained cell growth in culture and minimal tumor growth inhibition in cell line xenograft mouse models (PMID: 28396313). 28396313
MET Y1230H Advanced Solid Tumor predicted - sensitive Altiratinib Preclinical Actionable In a preclinical study, Altiratinib (DCC-2701) inhibited activity of MET Y1230H in an in vitro kinase assay (PMID: 26285778). 26285778
MET Y1230H Advanced Solid Tumor predicted - resistant Savolitinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing mouse MET Y1228H (corresponds to MET Y1230H in humans) were resistant to treatment with Savolitinib (AZD6094), demonstrating sustained cell growth in culture (PMID: 28396313). 28396313