About IDH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
IDH1 c.395G>T, p.(Arg132Leu)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 6
Benign evidence criteria: 0
Pathogenic criteria applied · 6
PS3Strong
PS3 · strong
R132L recombinant protein was directly tested and demonstrated gain-of-function neomorphic enzymatic activity, catalyzing NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (PMID:19935646). Independently, an IDH1 R132L glioma tumor sample was directly analyzed and showed markedly elevated (R)-2HG levels (>500-fold above wild-type; PMID:21326614). A third study confirmed that R132L mutant enzyme is biochemically targetable by the mutant-specific inhibitor AG-120 (ivosidenib) with IC50 of 13 nM (PMID:29670690). These represent at least two independent publications with variant-specific experimental functional data.
PM1Moderate
PM1 · moderate
The variant affects codon Arg132, the critical active-site residue of IDH1 and a statistically significant mutational hotspot (cancerhotspots.org). This residue is located in the enzyme's catalytic domain where it forms hydrogen bonds with the α- and β-carboxyl groups of isocitrate. All cancer-associated IDH1 mutations cluster at this single residue, defining it as a well-characterized functional domain where missense variation is established as pathogenic.
PM2Supporting
PM2 · supporting
This variant is absent from all population databases, including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes). The allele frequency of 0.0% is well below the PM2 threshold of <0.1% for a dominant disorder gene with no VCEP/CSPEC override.
PM5Moderate
PM5 · moderate
Multiple different missense variants at the same residue (Arg132) have been established as pathogenic. Arg132His (R132H), Arg132Cys (R132C), Arg132Ser (R132S), and Arg132Gly (R132G) are well-documented pathogenic substitutions in glioma and AML (PMID:19246647). R132H alone accounts for ~91% of IDH1 mutations in glioma. The presence of multiple pathogenic missense variants at this same codon supports PM5 at moderate strength.
PP3Supporting
PP3 · supporting
Multiple in silico predictors support a deleterious effect. REVEL score is 0.835 (deleterious; above the 0.75 threshold). BayesDel score is 0.402 (intermediate). SpliceAI predicts no significant splice impact (max delta score 0.10), consistent with the missense mechanism rather than splicing disruption. The REVEL score in the high-confidence deleterious range supports PP3 at supporting level.
PP5Supporting
PP5 · supporting
This variant has been reported in ClinVar as Pathogenic by CeGaT Center for Human Genetics Tuebingen (criteria provided, single submitter; ClinVar Variation ID: 375889). While the submission is from a clinical testing laboratory with criteria provided, the review status is 'single submitter' without expert panel review, limiting the weight to supporting level.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 strong, PM1 moderate, PM2 supporting, PM5 moderate, PP3 supporting, PP5 supporting; combination = 1 strong + 2 moderate + 3 supporting, which maps to Pathogenic.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.100 maximum delta
Recorded SpliceAI maximum delta score: 0.100. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
1 reported laboratory submissions
1 Pathogenic. ClinVar API review status: criteria provided, single submitter.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
159 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV61615420, n = 159 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 6 met · 16 not met · 0 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
PS3 (strong): Recombinant R132L protein directly tested in purified enzyme assay demonstrated gain-of-function neomorphic activity, catalyzing NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (PMID:19935646). Independently, a glioma sample harboring IDH1 R132L showed markedly elevated (R)-2HG levels on direct tissue analysis (PMID:21326614).
PM1 (moderate): The variant affects codon Arg132, the critical active-site residue and a statistically significant mutational hotspot. All cancer-associated IDH1 mutations cluster at this single residue, defining it as a well-characterized functional domain.
PM2 (supporting): This variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada, consistent with a rare pathogenic variant.
PM5 (moderate): Multiple different missense variants at the same residue (R132H, R132C, R132S, R132G) are well-established as pathogenic in glioma and AML (PMID:19246647).
PP3 (supporting): REVEL score of 0.835 is in the high-confidence deleterious range, supporting a pathogenic effect.
PP5 (supporting): ClinVar reports this variant as Pathogenic (Variation ID 375889; criteria provided, single submitter).
No criteria match.
Met · 6
PS3 StrongR132L recombinant protein was directly tested and demonstrated gain-of-function neomorphic enzymatic activity, catalyzing NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (PMID:19935646). Independently, an IDH1 R132L glioma tumor sample was directly analyzed and showed markedly elevated (R)-2HG levels (>500-fold above wild-type; PMID:21326614). A third study confirmed that R132L mutant enzyme is biochemically targetable by the mutant-specific inhibitor AG-120 (ivosidenib) with IC50 of 13 nM (PMID:29670690). These represent at least two independent publications with variant-specific experimental functional data. Details ▾Hide ▴
Evidence considered
- PMID:19935646: Recombinant R132L protein directly tested
- gain-of-function NADPH-dependent reduction of αKG to (R)-2HG confirmed by purified enzyme assay
- PMID:21326614: R132L glioma tumor tissue directly analyzed
- markedly elevated (R)-2HG levels confirmed by LC-MS/MS in patient sample
- PMID:29670690: R132L mutant enzyme directly profiled
- IC50=13nM for mutant-specific inhibitor AG-120
- confirming neomorphic active-site conformation
Sources
PM1 ModerateThe variant affects codon Arg132, the critical active-site residue of IDH1 and a statistically significant mutational hotspot (cancerhotspots.org). This residue is located in the enzyme's catalytic domain where it forms hydrogen bonds with the α- and β-carboxyl groups of isocitrate. All cancer-associated IDH1 mutations cluster at this single residue, defining it as a well-characterized functional domain where missense variation is established as pathogenic. Details ▾Hide ▴
Evidence considered
- cancerhotspots.org: statistically significant hotspot at R132
- PMID:19935646: R132 is the active-site residue
- all cancer-associated IDH1 mutations occur at this single residue
- PMID:19246647: all 130 IDH1 mutations detected across 321 gliomas were at amino acid residue 132
- PMID:21326614: R132 mutations are specific to the enzyme active site
Sources
PM2 SupportingThis variant is absent from all population databases, including gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes). The allele frequency of 0.0% is well below the PM2 threshold of <0.1% for a dominant disorder gene with no VCEP/CSPEC override. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent
- gnomAD v4.1: absent
- gnomAD-Canada v1.0: absent
Sources
PM5 ModerateMultiple different missense variants at the same residue (Arg132) have been established as pathogenic. Arg132His (R132H), Arg132Cys (R132C), Arg132Ser (R132S), and Arg132Gly (R132G) are well-documented pathogenic substitutions in glioma and AML (PMID:19246647). R132H alone accounts for ~91% of IDH1 mutations in glioma. The presence of multiple pathogenic missense variants at this same codon supports PM5 at moderate strength. Details ▾Hide ▴
Evidence considered
- PMID:19246647: R132H (91%)
- R132C (6/130)
- R132G (5/130)
- R132S (1/130) all detected as heterozygous mutations in gliomas
- all at amino acid residue 132
- PMID:21326614: R132H
- R132C
- R132S
- R132L
- R132G listed as recurrent glioma-derived IDH1 mutations
Sources
PP3 SupportingMultiple in silico predictors support a deleterious effect. REVEL score is 0.835 (deleterious; above the 0.75 threshold). BayesDel score is 0.402 (intermediate). SpliceAI predicts no significant splice impact (max delta score 0.10), consistent with the missense mechanism rather than splicing disruption. The REVEL score in the high-confidence deleterious range supports PP3 at supporting level. Details ▾Hide ▴
Evidence considered
- REVEL: 0.835 (deleterious
- >0.75 threshold)
- BayesDel: 0.402 (intermediate)
- SpliceAI: max delta 0.10 (no splice impact predicted)
Sources
PP5 SupportingThis variant has been reported in ClinVar as Pathogenic by CeGaT Center for Human Genetics Tuebingen (criteria provided, single submitter; ClinVar Variation ID: 375889). While the submission is from a clinical testing laboratory with criteria provided, the review status is 'single submitter' without expert panel review, limiting the weight to supporting level. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 375889: Pathogenic
- criteria provided
- single submitter (CeGaT Center for Human Genetics Tuebingen)
Sources
Not met · 16 · evaluated, threshold not reached
PS1 No evidence was identified that the same amino acid change (p.Arg132Leu) has been previously established as pathogenic through a different nucleotide change. The c.395G>T substitution is the only coding change producing p.Arg132Leu from the Arg132 codon (CGT→CTT). Details ▾Hide ▴
Evidence considered
- c.395G>T is the sole nucleotide change producing p.Arg132Leu from CGT
PS2 No de novo data were identified for this variant. No confirmed de novo observation (with maternity and paternity confirmed) is available in the case evidence. Details ▾Hide ▴
Still missing
- No de novo testing data available
PS4 No germline case-control data demonstrating statistically significant enrichment of this variant in affected individuals versus controls was identified. The variant is well-documented in somatic cancers (COSMIC n=159), but somatic prevalence does not satisfy germline PS4 criteria. No publication provided variant-specific germline case counts with appropriate controls. Details ▾Hide ▴
Evidence considered
- COSMIC: observed 159 times in somatic cancers
- no germline case-control data
Still missing
- No germline case-control enrichment data available
PM6 No de novo data were identified for this variant. No confirmed de novo observation (with maternity and paternity confirmed) is available in the case evidence. Details ▾Hide ▴
Still missing
- No de novo testing data available
PP1 No co-segregation data were identified for this variant. No family studies demonstrating segregation with disease are available in the evidence. Details ▾Hide ▴
Still missing
- No segregation data available
PP2 PP2 requires a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. For IDH1, the disease mechanism is a highly specific gain-of-function restricted to codon R132 (and rarely R100). The gene does not harbor pathogenic missense variants broadly distributed across its coding sequence; benign missense variation at non-hotspot positions does not clearly satisfy the PP2 criterion. The ultra-restricted mutational spectrum of IDH1 distinguishes it from typical PP2-eligible genes. Details ▾Hide ▴
Evidence considered
- IDH1 pathogenic missense variants are restricted almost entirely to codon R132
- the gene does not have a broad spectrum of disease-causing missense variants
PP4 No phenotype or clinical data for the proband were available in the case evidence. PP4 requires that the patient's phenotype or family history is highly specific for a disease with a single genetic etiology, which cannot be assessed without clinical information. Details ▾Hide ▴
Still missing
- No proband phenotype data available
BA1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency is 0.0%, far below the BA1 threshold of >1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (AF=0)
- gnomAD v4.1: absent (AF=0)
- gnomAD-Canada v1.0: absent (AF=0)
Sources
BS1 This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency is 0.0%, far below the BS1 threshold of >0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: absent (AF=0)
- gnomAD v4.1: absent (AF=0)
- gnomAD-Canada v1.0: absent (AF=0)
Sources
BS2 No data were available demonstrating observation of this variant in healthy adults. The variant is absent from all population databases, and no control cohort data were provided. Details ▾Hide ▴
Still missing
- No observation in healthy adult controls
BS3 Well-established functional studies demonstrate a deleterious gain-of-function effect, not a benign effect. Recombinant R132L protein catalyzes NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate (PMID:19935646). Tumor tissue with R132L shows markedly elevated (R)-2HG (PMID:21326614). These findings support pathogenicity, not benign impact. Details ▾Hide ▴
Evidence considered
- PMID:19935646: R132L gains neomorphic enzymatic activity producing (R)-2HG
- PMID:21326614: R132L tumor tissue shows elevated (R)-2HG
Sources
BS4 No segregation data were available. BS4 requires lack of segregation with disease in affected family members, which cannot be assessed without family study data. Details ▾Hide ▴
Still missing
- No segregation data available
BP2 No evidence was available demonstrating that this variant has been observed in trans with a pathogenic variant. No phase data or co-occurrence data were provided. Details ▾Hide ▴
Still missing
- No phase/co-occurrence data available
BP4 Multiple in silico predictors support a deleterious effect, not a benign effect. REVEL score is 0.835 (deleterious), which contradicts BP4. BP4 requires multiple lines of computational evidence suggesting no impact, which is not the case here. Details ▾Hide ▴
Evidence considered
- REVEL: 0.835 (deleterious
- contradicts benign prediction)
- BayesDel: 0.402 (intermediate)
Sources
revelbayesdel
BP5 No evidence was identified that this variant has been found in a case with an alternate molecular basis for disease. No co-occurring pathogenic variant data were provided. Details ▾Hide ▴
Still missing
- No co-occurrence data with alternate molecular cause
BP6 ClinVar reports this variant as Pathogenic, not benign. BP6 requires a reputable source to classify the variant as benign, which is not the case here. Details ▾Hide ▴
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_005896.3:c.395G>T (p.Arg132Leu) is a missense substitution. It does not fall into the generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. The generic PVS1 decision framework (PMC6185798) does not apply to this variant class. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution (c.395G>T
- p.Arg132Leu)
- not a null variant
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
BP1 N/ABP1 applies to missense variants in genes where primarily truncating variants cause disease. IDH1-associated cancers are driven by gain-of-function missense mutations at codon R132, not by loss-of-function truncating variants. Truncating variants in IDH1 would not be expected to produce the neomorphic 2-HG-producing activity. BP1 is not applicable when the disease mechanism is gain-of-function via missense rather than loss-of-function via truncation. Details ▾Hide ▴
Evidence considered
- IDH1 disease mechanism is gain-of-function missense
- not loss-of-function truncation
BP7 N/AThis is a missense variant (c.395G>T, p.Arg132Leu), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous
PS5 N/ASkipped per adjudication directive. PS5 is trivially not applicable for this variant assessment. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- IDH1
- Transcript
- NM_005896.3
- Coding (HGVS c.)
- NM_005896.3:c.395G>T
- Protein (HGVS p.)
- NP_005887.2:p.(Arg132Leu)
- GRCh38
- chr2:208248388 C>A
- GRCh37
- chr2:209113112 C>A
- ClinVar
- 375889, 156444
- COSMIC
- COSV61615420
Gene diagram
Every interpreted variant in IDH1, mapped onto the exon structure of NM_005896.3. Select a row to find it on the plot.
IDH1NM_005896.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in IDH1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.835
- BayesDel
- 0.402
How the predictions were used
PP3 SupportingMultiple in silico predictors support a deleterious effect. REVEL score is 0.835 (deleterious; above the 0.75 threshold). BayesDel score is 0.402 (intermediate). SpliceAI predicts no significant splice impact (max delta score 0.10), consistent with the missense mechanism rather than splicing disruption. The REVEL score in the high-confidence deleterious range supports PP3 at supporting level. Details ▾Hide ▴
Evidence considered
- REVEL: 0.835 (deleterious
- >0.75 threshold)
- BayesDel: 0.402 (intermediate)
- SpliceAI: max delta 0.10 (no splice impact predicted)
Sources
BP4 Multiple in silico predictors support a deleterious effect, not a benign effect. REVEL score is 0.835 (deleterious), which contradicts BP4. BP4 requires multiple lines of computational evidence suggesting no impact, which is not the case here. Details ▾Hide ▴
Evidence considered
- REVEL: 0.835 (deleterious
- contradicts benign prediction)
- BayesDel: 0.402 (intermediate)
Sources
revelbayesdel
BP7 N/AThis is a missense variant (c.395G>T, p.Arg132Leu), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.835. BayesDel score = 0.402059.
9 paper records listed. 4 cited in the classification.
Cited in the classification
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PMID 19246647 ↗IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas.Watanabe T et al. · 2009 AprScreening of 321 gliomas for IDH1 mutations identified 130 mutations, all at amino acid residue 132. Detected substitutions were R132H (91%), R132C (6/130), R132G (5/130), and R132S (1/130). R132L (CGT>CTT) was not identified in this cohort; only CGT>CAT, CGT>TGT, CGT>GGT, and CGT>AGT were observed.→ PM1 → PM5 Does not name this variant
Source detail
six mutations were CGT→TGT (Arg→Cys), five were CGT→GGT (Arg→Gly), and one was CGT→AGT (Arg→Ser).
Location Results; Frequency of IDH1 Mutations
-
PMID 19935646 ↗Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.Dang L et al. · 2009 Dec 10Recombinant R132L mutant IDH1 protein was directly tested and demonstrated gain-of-function neomorphic enzymatic activity, catalyzing NADPH-dependent reduction of α-ketoglutarate to the oncometabolite (R)-2-hydroxyglutarate, confirming that the leucine substitution at R132 shares the pathogenic mechanism with other R132 mutants.→ PS3 → PM1 Names this variant
Source detail
Similar to R132H mutant protein, R132C, R132L, and R132S mutations all result in a gain-of-function for NADPH-dependent reduction of αKG.
Location Results; Supplementary Figure 4; Methods Summary
Context Recombinant IDH1 protein purified from E. coli; NADPH-dependent αKG reduction assay; U87MG and LN-18 glioblastoma cell lines
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PMID 21326614 ↗2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP-dependent isocitrate dehydrogenase mutations.Jin G et al. · 2011 Feb 4A glioma tumor sample harboring the IDH1 R132L mutation was directly analyzed for 2-hydroxyglutarate levels. The R132L tumor showed markedly elevated (R)-2HG (54.4 vs. 0.1 mg/g protein in IDH-wildtype tumors, p<0.001), demonstrating that the neomorphic activity is present in patient tissue.→ PS3 → PM1 → PM5 Names this variant
Source detail
We analyzed 2HG in 12 glioma samples, including samples containing IDH1 R132H, IDH1 R132L, IDH2 R172K, IDH2 R172M or no IDH mutations... all tumors containing IDH mutations had markedly elevated (R)-2-hydroxyglutarate compared to tumors without IDH mutations (54.4 vs. 0.1 mg 2HG/g protein, p<0.001).
Location Results (Fig. 3c); Discussion
Context Patient glioma tissue samples; LC-MS/MS quantification of (R)-2-hydroxyglutarate
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PMID 29670690 ↗Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.AG-120 (ivosidenib), a mutant IDH1 inhibitor, was biochemically profiled against multiple IDH1-R132 mutants. R132L enzyme was directly tested with an IC50 of 13 nM, confirming the drug targets the neomorphic active-site conformation of R132L.→ PS3 Names this variant
Source detail
IDH1-R132L 13
Location Table 3
Context Biochemical enzyme assay; recombinant mIDH1-R132 homodimer; HT1080 chondrosarcoma cell line (R132C)
Other recorded publications
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PMID 23630074 ↗What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer.Review article discussing IDH mutations across cancer types. R132L is listed among IDH1 substitutions in Table 1 (cholangiocarcinoma section: IDH1 R132L/G). The review summarizes the gain-of-function mechanism of IDH mutations and 2-HG production, but does not present primary data specific to R132L.Names this variant
Quoted passage
IDH1 R132L/G
Table 1; cholangiocarcinoma section
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PMID 29860938 ↗Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML.Phase 1 clinical trial of ivosidenib in IDH1-mutated AML. R132L is included within the combined group 'R132G/L/S' representing 14-17% of patients in the dose-expansion phase. No R132L-specific efficacy or safety outcomes were reported separately.Names this variant
Quoted passage
R132G/L/S
Table 1 (R132G/L/S group)
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PMID 26061751 ↗Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.Cancer Genome Atlas Research Network et al. · 2015Comprehensive genomic analysis of 293 lower-grade gliomas by TCGA. IDH1 and IDH2 mutations are discussed as defining alterations in lower-grade gliomas, categorized broadly as IDH-mutant versus IDH-wildtype. NM_005896.3:c.395G>T (R132L) was not specifically identified or reported in this paper.Does not name this variant
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PMID 33772213 ↗IDH-mutant gliomas with additional class-defining molecular events.Ahrendsen JT et al. · 2021Study of IDH-mutant gliomas with additional class-defining molecular events. Of 18 cases identified, IDH1 mutations were R132H (15/18), R132S (2/18), and R132C (1/18). NM_005896.3:c.395G>T (R132L) was not identified in this case series.Does not name this variant
Quoted passage
All IDH mutations involved IDH1, the most common being R132H (15/18 cases). IDH1 R132S mutations were observed in two cases, while IDH1 R132C was seen in one case.
Table 1; Results
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PMID 27993330 ↗Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists.AMP/ASCO/CAP joint consensus guideline for interpretation of somatic sequence variants in cancer. This is a standards and guidelines document that does not report primary data on NM_005896.3:c.395G>T (R132L).Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.100
Open source ↗
ClinVar
1 Pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/375889/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-209113112-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-208248388-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-208248388-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_005896.3%3Ac.395G…
- OncoKB ↗www.oncokb.org/gene/IDH1/R132L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=153664069
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (1 clinical laboratory). (ClinVarID = 375889)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.10). REVEL score = 0.835. BayesDel score = 0.402059.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV61615420, n = 159 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.