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Gene RET
Variant L56M
Impact List missense
Protein Effect no effect
Gene Variant Descriptions RET L56M lies within the extracellular domain of the Ret protein (UniProt.org). L56M does not effect Ret extracellular domain secretion (PMID: 20473317), and results in similar phosphorylation of Ret, Stat3, and Erk to wild-type Ret in culture (PMID: 31649719).
Associated Drug Resistance
Category Variants Paths

RET mutant RET L56M

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Transcript NM_020975.6
gDNA chr10:g.43100551C>A
cDNA c.166C>A
Protein p.L56M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001406767.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406781.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406782.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406761.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406791.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406790.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406768.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406771.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020975.5 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406780.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406788.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406778.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406760.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020975 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406765.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406787.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001355216.1 chr10:g.43106436C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406759.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406773.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020630.7 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406777.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406743.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406789.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020630 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406783.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406766.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001355216.2 chr10:g.43106436C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406769.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406770.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020975.6 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_020630.5 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406764.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406776.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406774.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406775.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406744.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406762.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406763.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406779.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406786.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406772.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38
NM_001406785.1 chr10:g.43100551C>A c.166C>A p.L56M RefSeq GRCh38/hg38

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  • Separate multiple filter terms with a space. Any order may be used (i. e. 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 on a longer phrase with spaces (i.e. "mtor c1483f")

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET mutant lung non-small cell carcinoma predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated in non-small cell lung cancer (NSCLC) patients harboring RET mutations, and resulted in an objective response rate (ORR) of 63% (20/32, 1 complete response (CR)) and disease control rate (DCR) of 91% in pretreated patients, and an ORR of 76% (19/25, 1 CR) and DCR of 92% with median duration of response not reached in treatment-naive patients, and an overall CNS DCR of 100% (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant pheochromocytoma predicted - sensitive Sunitinib Case Reports/Case Series Actionable In a Phase II trial (SNIPP), a patient with pheochromocytoma harboring a germline RET mutation achieved a partial response to treatment with Sutent (sunitinib), and demonstrated a 64% reduction in tumor volume and remained on treatment for over 7 years (PMID: 31105270). 31105270
RET mutant medullary thyroid 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 medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-121) that supported FDA approval, Retevmo (selpercatinib) treatment was safe in pediatric patients of 2 years or older with solid tumors (8 medullary thyroid cancer, 2 papillary thyroid cancer, 1 osteosarcoma) harboring RET fusion (n=2) or mutations (n=9), and resulted in unconfirmed partial responses in 4 patients, stable disease in 6 patients (two lasting >/=16 weeks) (JCO 39, 10009-10009(2021); NCT03899792). detail... detail... detail...
RET mutant medullary thyroid carcinoma sensitive Selpercatinib Guideline Actionable Retevmo (selpercatinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant medullary thyroid carcinoma sensitive Selpercatinib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55), with five complete and 33 partial responses, in adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations who were previously treated, while patients who had not been previously treated demonstrated an ORR of 73% (64/88), with ten complete and 54 partial responses (PMID: 32846061; NCT03157128). detail... detail... 32846061
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 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
RET mutant lung non-small cell carcinoma unknown unspecified immune checkpoint inhibitor Clinical Study - Cohort Actionable In a retrospective clinical study, patients with non-small cell lung cancer harboring rare targetable drivers (RTD) (BRAF, ERBB2/3, RET, MET, ROS1, NTRK) who received immune checkpoint inhibitors (ICI) achieved longer median overall survival (mOS) (32 vs 13 mo, p=0.01) compared to those who did not receive ICI, mOS was 44.9 mo in a patient harboring RET mutation, although RTD type was not associated with OS in a univariate analysis (PMID: 30268448). 30268448
RET mutant Advanced Solid Tumor predicted - sensitive EP0031 Phase Ib/II Actionable In a Phase I/II trial (KL400-I/II-01), EP0031 treatment was well tolerated and demonstrated preliminary activity in patients with advanced solid tumors harboring mutations in RET, resulting in an objective response rate of 64%, with responses being observed in patients with non-small cell lung cancer, medullary thyroid cancer and pancreatic cancer (J Clin Oncol 41, 2023 (suppl 16; abstr 3007); NCT05265091). detail...
RET mutant medullary thyroid carcinoma sensitive Everolimus Phase II Actionable In a Phase II 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; NCT01118065). 26294908
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 medullary thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines for adult or pediatric patients 12 years or older with advanced or metastatic medullary thyroid gland carcinoma harboring RET mutations (PMID: 31549998, PMID: 35491008; ESMO.org). 31549998 detail... 35491008
RET mutant medullary thyroid carcinoma sensitive Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated and resulted in an overall response rate (ORR) of 60% (3/55) in patients with advanced or metastatic medullary thyroid cancer harboring RET mutations who received prior treatments, ORR was 60% (32/53) in patients with prior therapies and 71% (15/21) in treatment-naive patients (PMID: 34118198; NCT03037385). 34118198
RET mutant medullary thyroid carcinoma sensitive Pralsetinib Guideline Actionable Gavreto (pralsetinib) is included in guidelines (category 2B) for patients with medullary thyroid carcinoma harboring RET mutations (NCCN.org). detail...