Gene Variant Detail

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Gene RET
Variant G691S
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions RET G691S lies within the cytoplasmic domain of the Ret protein (UniProt.org). G691S results in increased Ret phosphorylation and activation of downstream signaling pathways in response to Gdnf, and increased invasion in cultured cells (PMID: 16357163, PMID: 19561646).
Associated Drug Resistance

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Transcript NM_020975
gDNA chr10:g.43114671G>A
cDNA c.2071G>A
Protein p.G691S
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_020630 chr10:g.43114671G>A c.2071G>A p.G691S RefSeq GRCh38/hg38
NM_020975 chr10:g.43114671G>A c.2071G>A p.G691S RefSeq GRCh38/hg38

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET G691S Advanced Solid Tumor predicted - sensitive Dovitinib Case Reports/Case Series Actionable In a Phase I clinical trial, two patients with germline RET G691S mutations demonstrated sensitivity to Dovitinib (TKI258) treatment (PMID: 25103625). 25103625
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET act mut lung non-small cell carcinoma sensitive Ponatinib Preclinical - Cell culture Actionable In a preclinical study, Iclusig (ponatinib) inhibited RET phosphorylation and reduced viability of non-small cell lung cancer cells with RET activating mutations (Cancer Res April 15, 2013 73; 2084). detail...
RET mutant Advanced Solid Tumor sensitive Ponatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of cancer cell lines harboring RET mutations in cultured and in cell line xenograft models (PMID: 23526464). 23526464
RET mutant colorectal cancer sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) demonstrated efficacy in RET mutant positive colorectal cancer cell lines (PMID: 23811235). 23811235
RET mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (60 vs 20 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RET mutations (PMID: 27525386). 27525386
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib FDA approved Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate of 56% (31/55) in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations (Ann Oncol, Oct 2019, 30 (Suppl 5): v933, Abstract LBA93; NCT03157128). detail... detail...
RET mutant thyroid gland medullary carcinoma sensitive Selpercatinib Phase I Actionable In a Phase I trial, Retevmo (selpercatinib) treatment resulted in partial response in 14% (2/14) and tumor reduction in 79% (11/14) of RET mutant thyroid medullary cancer patients (J Clin Oncol 36, 2018 (suppl; abstr 102); NCT03157128). detail...
RET mutant thyroid gland medullary carcinoma sensitive Everolimus Phase II Actionable In a Phase II clinical trial, Afinitor (everolimus) treatment resulted in stable disease in 71% (5/7) of medullary thyroid cancer patients, including patients harboring RET mutations, with median progression-free survival of 33 weeks (PMID: 26294908). 26294908
RET mutant cancer sensitive Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) inhibited wild-type RET and RET mutations to prevent cell proliferation in cell culture (PMID: 17664273). 17664273
Molecular Profile Protein Effect Treatment Approaches
RET G691S gain of function