IDH1 R132L

Loading variant…

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Acute Myeloid Leukemia2
IDH1 R132 AND IDH1 R132L	(oncogenic)	Oncogenic	B	Supports Oncogenicity	3	submitted	EID12898 In the phase 3 AGILE trial enrolling patients with newly diagnosed IDH1-mutated AML who were ineligible for intensive induction chemotherapy, IDH1 R132 mutations (confirmed by FDA-approved Abbott Real… (full text at CIViC) PMID 35443108 · Montesinos et al., 2022 · Open in CIViC	civic
IDH1 R132L	Ivosidenib	Predictive	B	Supports Sensitivity Response	—	rejected	EID2021 In a clinical study of 17 relapsed or refractory AML patients harboring IDH1 mutations, patients were associated with response to AG-120 monotherapy; 4/7 patients who achieved a response experienced c… (full text at CIViC) PMID 25583779 · 2015 · Open in CIViC	civic

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Acute Myeloid Leukemia2

IDH1 R132 AND IDH1 R132L

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID12898

In the phase 3 AGILE trial enrolling patients with newly diagnosed IDH1-mutated AML who were ineligible for intensive induction chemotherapy, IDH1 R132 mutations (confirmed by FDA-approved Abbott Real… (full text at CIViC)

PMID 35443108 · Montesinos et al., 2022 · Open in CIViC

civic

IDH1 R132L

Ivosidenib

Predictive

Supports Sensitivity Response

—

rejected

EID2021

In a clinical study of 17 relapsed or refractory AML patients harboring IDH1 mutations, patients were associated with response to AG-120 monotherapy; 4/7 patients who achieved a response experienced c… (full text at CIViC)

PMID 25583779 · 2015 · Open in CIViC

civic

Variation	Clinical significance	Review status	Stars	Conditions	Origin	Submitters	Last evaluated	Source
375889	Pathogenic	criteria provided, single submitter	1	Neoplasm; Astrocytoma IDH-mutant	germline/somatic	3	Apr 01, 2025	clinvar

Variation

Clinical significance

Review status

Stars

Conditions

Origin

Submitters

Last evaluated

Source

375889

Pathogenic

criteria provided, single submitter

Neoplasm; Astrocytoma IDH-mutant

germline/somatic

Apr 01, 2025

clinvar

Low Grade Glioma1
IDH1 R132C OR IDH1 R132H OR IDH1 R132L OR IDH1 R132G OR IDH1 R132S	Vorasidenib	Predictive	A	Supports Sensitivity Response	5	accepted	EID11508 This phase 3 clinical trial was conducted to assess the progression free survival in patients with IDH-mutant gliomas treated with Vorasidenib, an oral brain-penetrant inhibitor, which showed prelimin… (full text at CIViC) PMID 37272516 · Mellinghoff et al., 2023 · Open in CIViC	civic

Low Grade Glioma1

IDH1 R132C OR IDH1 R132H OR IDH1 R132L OR IDH1 R132G OR IDH1 R132S

Vorasidenib

Predictive

Supports Sensitivity Response

accepted

EID11508

This phase 3 clinical trial was conducted to assess the progression free survival in patients with IDH-mutant gliomas treated with Vorasidenib, an oral brain-penetrant inhibitor, which showed prelimin… (full text at CIViC)

PMID 37272516 · Mellinghoff et al., 2023 · Open in CIViC

civic

Myelodysplastic Syndrome1
IDH1 R132L	(oncogenic)	Oncogenic	C	Supports Oncogenicity	2	submitted	EID13304 Lin et al. analyzed 168 patients with de novo myelodysplastic syndrome (MDS) and identified IDH1 mutations in 7/168 (4.2%), including R132H (n=3), R132C (n=3), and R132L (n=1). In analyses of paired M… (full text at CIViC) PMID 23996483 · Lin et al., 2014 · Open in CIViC	civic

Myelodysplastic Syndrome1

IDH1 R132L

(oncogenic)

Oncogenic

Supports Oncogenicity

submitted

EID13304

Lin et al. analyzed 168 patients with de novo myelodysplastic syndrome (MDS) and identified IDH1 mutations in 7/168 (4.2%), including R132H (n=3), R132C (n=3), and R132L (n=1). In analyses of paired M… (full text at CIViC)

PMID 23996483 · Lin et al., 2014 · Open in CIViC

civic

Brain Glioma2unmapped disease
IDH1 R132L	Temozolomide	Predictive	B	Supports Sensitivity Response	—	rejected	EID2017 IDH1 mutations at R132H are the most frequent mutations accounting for 70- 90% of all IDH1 mutations in secondary glioblastoma and 5% of primary glioblastomas. PMID 18772396 · Parsons et al., 2008 · Open in CIViC	civic
IDH1 R132L	Temozolomide	Predictive	B	Supports Sensitivity Response	—	submitted	EID2018 In a study of 189 low-grade gliomas, IDH (IDH1 or IDH2) mutations were found in 132 patients (70%). IDH mutations were associated with improved rate of response to temozolomide compared to wildtype ID… (full text at CIViC) PMID 20975057 · Houillier et al., 2010 · Open in CIViC	civic

Brain Glioma2unmapped disease

IDH1 R132L

Temozolomide

Predictive

Supports Sensitivity Response

—

rejected

EID2017

IDH1 mutations at R132H are the most frequent mutations accounting for 70- 90% of all IDH1 mutations in secondary glioblastoma and 5% of primary glioblastomas.

PMID 18772396 · Parsons et al., 2008 · Open in CIViC

civic

IDH1 R132L

Temozolomide

Predictive

Supports Sensitivity Response

—

submitted

EID2018

In a study of 189 low-grade gliomas, IDH (IDH1 or IDH2) mutations were found in 132 patients (70%). IDH mutations were associated with improved rate of response to temozolomide compared to wildtype ID… (full text at CIViC)

PMID 20975057 · Houillier et al., 2010 · Open in CIViC

civic

Unmapped disease2unmapped disease
IDH1 R132L	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID13305 Dang et al. demonstrated that IDH1 R132L confers a neomorphic gain of enzymatic function. Recombinant R132L IDH1 acquired NADPH-dependent reduction of α-ketoglutarate, whereas wild-type IDH1 lacked me… (full text at CIViC) PMID 19935646 · Dang et al., 2009 · Open in CIViC	civic
IDH1 R132L	(functional)	Functional	D	Supports Neomorphic	3	submitted	EID13306 Pusch et al. demonstrated variant-specific neo-enzymatic activity of IDH1 R132L. Purified R132L protein had a reported KM of 11.8 uM for α-ketoglutarate, and HEK293T cells expressing R132L produced si… (full text at CIViC) PMID 24529257 · Pusch et al., 2014 · Open in CIViC	civic

Unmapped disease2unmapped disease

IDH1 R132L

(functional)

Functional

Supports Gain Of Function

submitted

EID13305

Dang et al. demonstrated that IDH1 R132L confers a neomorphic gain of enzymatic function. Recombinant R132L IDH1 acquired NADPH-dependent reduction of α-ketoglutarate, whereas wild-type IDH1 lacked me… (full text at CIViC)

PMID 19935646 · Dang et al., 2009 · Open in CIViC

civic

IDH1 R132L

(functional)

Functional

Supports Neomorphic

submitted

EID13306

Pusch et al. demonstrated variant-specific neo-enzymatic activity of IDH1 R132L. Purified R132L protein had a reported KM of 11.8 uM for α-ketoglutarate, and HEK293T cells expressing R132L produced si… (full text at CIViC)

PMID 24529257 · Pusch et al., 2014 · Open in CIViC

civic

Evidence by cancer (8 items)

Clinical significance (1)