About FH
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
FH c.151C>T, p.(Arg51Trp)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PS3Supporting
PS3 · supporting
In one patient with pheochromocytoma, PCC tissue analysis of this variant revealed loss of heterozygosity at the FH locus and positive 2-SC (S-(2-succinyl)cysteine) immunostaining, confirming FH deficiency in the tumor and supporting a deleterious functional effect.
PM2Moderate
PM2 · moderate
This variant is extremely rare in population databases: gnomAD v2.1 allele frequency is 7.96e-06 (0.00080%, 2/251,290 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency is 2.48e-06 (0.00025%, 4/1,613,958 alleles, 0 homozygotes). Both are well below the 0.1% PM2 threshold for a rare disease gene.
PP3Supporting
PP3 · supporting
Multiple in silico tools predict a deleterious effect: REVEL score of 0.799 is in the pathogenic range. SpliceAI predicts no splice impact (max delta = 0.00), so the predicted effect is at the protein level.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
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 supporting, PM2 moderate, PP3 supporting; combination = 1 moderate + 2 supporting, which maps to VUS.
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
4 / 1,613,958 alleles
gnomAD v4.1: 4 / 1,613,958 alleles. Recorded AF 2.47838e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95893e-06; MAF= 0.00080%, 2/251290 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53339e-05; MAF= 0.00653%, 2/30612 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
4 Likely pathogenic · 1 Uncertain significance · 1 Pathogenic. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FH, an enzyme that converts fumarate to malate in the TCA cycle, is infrequently altered in cancer.
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV63818256, n = 2 times).
Cancer Hotspots
This variant does not lie 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.
29 criteria with recorded statuses: 3 met · 22 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
This missense variant (c.151C>T, p.Arg51Trp) is extremely rare in population databases (gnomAD v2.1 allele frequency 0.00080%, v4.1 allele frequency 0.00025%), meeting PM2 at moderate strength.
In one patient with pheochromocytoma, tumor tissue analysis revealed loss of heterozygosity at the FH locus and positive 2-SC immunostaining confirming FH deficiency, providing functional evidence at supporting strength (PS3_supporting).
Multiple in silico tools predict a deleterious effect (REVEL score 0.799), supporting a pathogenic role at the protein level (PP3_supporting).
The variant has been reported in ClinVar (VariationID 649446) as Likely pathogenic by multiple clinical laboratories (4 LP, 1 P, 1 VUS), but no expert panel review is available; PP5 is not met.
PVS1 is not applicable as this is a missense variant. PS4 is not met due to insufficient published case numbers. Remaining pathogenic and benign criteria are not met.
No criteria match.
Met · 3
PS3 SupportingIn one patient with pheochromocytoma, PCC tissue analysis of this variant revealed loss of heterozygosity at the FH locus and positive 2-SC (S-(2-succinyl)cysteine) immunostaining, confirming FH deficiency in the tumor and supporting a deleterious functional effect. Details ▾Hide ▴
Evidence considered
- LOH at FH locus in PCC tissue from a patient carrying c.151C>T
- Positive 2-SC immunostaining confirming FH enzymatic deficiency in tumor tissue
Still missing
- Functional evidence is from tumor tissue biomarker (indirect assay) in a single patient
- no controlled in vitro enzymatic assay or independent replication.
Sources
PM2 ModerateThis variant is extremely rare in population databases: gnomAD v2.1 allele frequency is 7.96e-06 (0.00080%, 2/251,290 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency is 2.48e-06 (0.00025%, 4/1,613,958 alleles, 0 homozygotes). Both are well below the 0.1% PM2 threshold for a rare disease gene. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.00080%
- 2/251
- 290 alleles
- 0 homozygotes
- gnomAD v4.1: AF = 0.00025%
- 4/1
- 613
- 958 alleles
- Highest subpopulation AF: South Asian 0.00653% (v2.1)
Sources
PP3 SupportingMultiple in silico tools predict a deleterious effect: REVEL score of 0.799 is in the pathogenic range. SpliceAI predicts no splice impact (max delta = 0.00), so the predicted effect is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.799 (pathogenic range)
- BayesDel score: 0.446
- SpliceAI max delta: 0.00 (no splicing impact predicted)
Still missing
- BayesDel score (0.446) is below the typical 0.5 pathogenic threshold
- REVEL alone supports deleterious prediction.
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No evidence of a different nucleotide change at c.151 predicted to produce the same amino acid substitution (p.Arg51Trp). Details ▾Hide ▴
Evidence considered
- No alternative nucleotide substitution at the same codon identified.
Still missing
- No ClinVar or literature data identifying a different nucleotide change at c.151 resulting in p.Arg51Trp.
PS2 No de novo report for NM_000143.4:c.151C>T was identified in the available literature or ClinVar submissions. Details ▾Hide ▴
Still missing
- No de novo testing data available.
PS4 Only one published case with variant-specific clinical detail (PCC at age 55, PMID 30877234). Insufficient case numbers to establish statistically significant enrichment over population controls. Additional cases may exist in clinical laboratory internal data but are not publicly accessible. Details ▾Hide ▴
Evidence considered
- One published case: PCC diagnosed at 55 years (Ben Aim et al. 2019)
- ClinVar submissions from multiple clinical laboratories but no aggregated case counts with phenotype details
Still missing
- No case-control data or statistically significant enrichment demonstrated.
- Clinical laboratory internal case counts not publicly available for independent review.
Sources
PM1 Residue 51 is located in the N-terminal Domain 1 of FH (residues 49-188), which is a structural domain without a characterized independent functional role. The variant does not fall within the fumarate lyase domain (exons 5-7) and is not in a statistically significant mutational hotspot per cancerhotspots.org. Details ▾Hide ▴
Evidence considered
- Residue 51 is in N-terminal Domain 1
- not in a critical catalytic domain
- Not a statistically significant hotspot at cancerhotspots.org
Still missing
- No evidence that residue 51 lies within a well-characterized critical functional domain.
Sources
PM5 No same-residue comparator variant with a different pathogenic amino acid change was identified. Automated PM5 candidate harvesting did not identify eligible comparators. Details ▾Hide ▴
Evidence considered
- No ClinVar entries for alternate pathogenic amino acid changes at Arg51.
Sources
pm5_candidates
PM6 No de novo report for this variant was identified in the available literature or ClinVar submissions. Details ▾Hide ▴
Still missing
- No parental testing data available.
PP1 No co-segregation data available. The only published case (PMID 30877234) provides no family segregation information. Details ▾Hide ▴
Still missing
- No family segregation studies available.
PP2 Although missense variants are the most common mutation type in FH (55%), there is insufficient evidence that the rate of benign missense variants in FH is low enough to satisfy PP2 under generic ACMG. Details ▾Hide ▴
Evidence considered
- FH missense variants represent 55% of reported mutations (Ajalla Aleixo et al. 2019).
Still missing
- No gene-specific missense constraint metric or benign missense rate data available for FH.
Sources
PP4 Pheochromocytoma alone is not a highly specific phenotype for FH-related disease; it is associated with multiple other genes (SDHx, VHL, RET, NF1, etc.). The patient phenotype does not meet the threshold for PP4. Details ▾Hide ▴
Evidence considered
- Single published case presented with PCC at age 55
- which is not sufficiently specific for FH.
Sources
PP5 ClinVar review status for this variant (VariationID 649446) is 'criteria provided, single submitter' with 0 expert panel submissions. PP5 requires ClinVar classification reviewed by expert panel (3-star) to apply at supporting strength. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely pathogenic
- review status 'criteria provided
- single submitter'
- Zero expert panel submissions (0 out of 7 total)
- No 3-star review status
Still missing
- No expert panel review in ClinVar.
Sources
BA1 gnomAD allele frequency (0.00080% v2.1, 0.00025% v4.1) is far below the 1% BA1 threshold for standing as a benign variant. Details ▾Hide ▴
BS1 gnomAD allele frequency (0.00080%) is below the 0.3% BS1 threshold for a variant too common to cause a rare disease. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF = 0.00080% (< 0.3% BS1 threshold)
- gnomAD v4.1 AF = 0.00025% (< 0.3% BS1 threshold)
Sources
BS2 No homozygous observations in gnomAD. No evidence of the variant being observed in a healthy adult individual in trans with a known pathogenic FH variant. Details ▾Hide ▴
Evidence considered
- Zero homozygotes in gnomAD v2.1 and v4.1.
Still missing
- No data on trans configurations or homozygous healthy adults.
Sources
BS3 No well-established in vitro or in vivo functional studies demonstrate no deleterious effect for this variant. The only available functional evidence (PMID 30877234) points toward pathogenicity (LOH + positive 2-SC staining). Details ▾Hide ▴
Evidence considered
- Only functional data available supports a deleterious effect (2-SC positive in tumor tissue)
Still missing
- No benign functional evidence available.
Sources
BS4 No evidence of non-segregation with disease in affected families. Details ▾Hide ▴
Still missing
- No segregation data available.
BP1 BP1 applies to missense variants in genes where only truncating variants cause disease. FH has numerous well-established pathogenic missense variants (missense mutations represent 55% of reported variants). BP1 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense mutations represent 55% of FH variants
- missense variants are a known disease mechanism in FH.
Sources
BP2 No observation of this variant in trans with a known pathogenic FH variant. Details ▾Hide ▴
Still missing
- No trans configuration data available.
BP4 Multiple in silico tools predict a deleterious effect (REVEL 0.799). SpliceAI predicts no splice impact (max delta = 0.00), but protein-level predictions contradict BP4. BP4 is not met when computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL 0.799 predicts deleterious effect
- contradicting BP4
- SpliceAI max delta = 0.00 (no benign splice prediction supporting BP4)
Sources
BP5 No strong evidence from other sources suggesting a benign role. The variant has been observed in a case with PCC and is absent from large population cohorts at significant frequency. Details ▾Hide ▴
No further detail was recorded.
BP6 ClinVar review status for this variant is 'criteria provided, single submitter' with 0 expert panel submissions. BP6 requires a 3-star expert panel classification of benign or likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Likely pathogenic (not benign)
- No expert panel review available
Still missing
- No expert panel classification available.
Sources
BP7 This is a missense variant (c.151C>T, p.Arg51Trp), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 is for synonymous variants only.
PS5 No different pathogenic variant at the same codon (Arg51) was identified from a clinically validated source. Details ▾Hide ▴
Still missing
- No alternate pathogenic variant identified at codon 51.
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense substitution (c.151C>T, p.Arg51Trp); PVS1 applies to null variants (nonsense, frameshift, canonical splice site) and this variant does not fall into those buckets. Details ▾Hide ▴
Evidence considered
- Missense variant in exon 2 does not qualify as a null variant under PVS1 framework (PMC6185798).
Sources
pvs1_variant_assessment
PM3 N/AFH-related disease (HLRCC) is autosomal dominant; PM3 applies to recessive disorders only. Details ▾Hide ▴
No further detail was recorded.
PM4 N/AVariant is a missense substitution; PM4 applies to protein length-altering variants (in-frame deletions/insertions, stop-loss). Details ▾Hide ▴
No further detail was recorded.
BP3 N/AVariant is a substitution; BP3 applies to in-frame deletions/insertions in repetitive regions. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- FH
- Transcript
- NM_000143.4
- Coding (HGVS c.)
- NM_000143.4:c.151C>T
- Protein (HGVS p.)
- NP_000134.2:p.(Arg51Trp)
- GRCh38
- chr1:241517298 G>A
- GRCh37
- chr1:241680598 G>A
- ClinVar
- 649446
- COSMIC
- COSV63818256
Gene diagram
Every interpreted variant in FH, mapped onto the exon structure of NM_000143.4. Select a row to find it on the plot.
FHNM_000143.4
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 FH
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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
4 / 1,613,958 alleles
AF 2.48e-06 · 0 homozygotes · FAF 3.65e-06
gnomAD v2.1
2 / 251,290 alleles
AF 7.96e-06 · 0 homozygotes · FAF 1.08e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.5e-06 · 4 / 1,613,958 alleles · 0 hom · FAF 3.7e-06
| South Asian2 / 91,074 | 2.2e-05 |
| Remaining individuals1 / 62,502 | 1.6e-05 |
| European (non-Finnish)1 / 1,180,012 | 8.5e-07 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 8e-06 · 2 / 251,290 alleles · 0 hom · FAF 1.1e-05
| South Asian2 / 30,612 | 6.5e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.47838e-06; MAF= 0.00025%, 4/1613958 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.19602e-05; MAF= 0.00220%, 2/91074 alleles, homozygotes = 0); grpmax FAF= 3.65e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95893e-06; MAF= 0.00080%, 2/251290 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53339e-05; MAF= 0.00653%, 2/30612 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.799
- BayesDel
- 0.447
How the predictions were used
PP3 SupportingMultiple in silico tools predict a deleterious effect: REVEL score of 0.799 is in the pathogenic range. SpliceAI predicts no splice impact (max delta = 0.00), so the predicted effect is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score: 0.799 (pathogenic range)
- BayesDel score: 0.446
- SpliceAI max delta: 0.00 (no splicing impact predicted)
Still missing
- BayesDel score (0.446) is below the typical 0.5 pathogenic threshold
- REVEL alone supports deleterious prediction.
Sources
BP4 Multiple in silico tools predict a deleterious effect (REVEL 0.799). SpliceAI predicts no splice impact (max delta = 0.00), but protein-level predictions contradict BP4. BP4 is not met when computational evidence supports pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL 0.799 predicts deleterious effect
- contradicting BP4
- SpliceAI max delta = 0.00 (no benign splice prediction supporting BP4)
Sources
BP7 This is a missense variant (c.151C>T, p.Arg51Trp), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 is for synonymous variants only.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.799. BayesDel score = 0.446505.
8 paper records listed. 1 cited in the classification.
Cited in the classification
-
PMID 30877234 ↗Targeted next-generation sequencing detects rare genetic events in pheochromocytoma and paraganglioma.Ben Aim L et al. · 2019 AugNM_000143.4:c.151C>T (p.Arg51Trp) detected in a patient with pheochromocytoma diagnosed at 55 years. Tumor analysis revealed loss of heterozygosity at the FH locus and positive 2-SC immunostaining, confirming FH deficiency and supporting classification of the variant as pathogenic.→ PS3 Names this variant
Source detail
the PCC tissue analysis revealed a LOH at the FH locus and positive 2-SC immunostaining, which are both in favour of the FH, p.Arg51Trp pathogenicity that can be, then, classified as pathogenic.
Location Results, paragraph on patients with two germline VOI; Discussion, paragraph on co-occurring variants
Context Tumor tissue immunohistochemistry (2-SC staining), LOH analysis in pheochromocytoma tissue from a 55-year-old patient
Other recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for interpretation of sequence variants. Provides the framework for variant classification criteria. No variant-specific data are included.Does not name this variant
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PMID 26700204 ↗Recurrent Mutations of Chromatin-Remodeling Genes and Kinase Receptors in Pheochromocytomas and Paragangliomas.Toledo RA et al. · 2016This study sequenced exomes/transcriptomes of 43 PPGL samples to identify novel variants in tyrosine kinase and chromatin-remodeling genes. NM_000143.4:c.151C>T was not identified in this paper.Does not name this variant
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PMID 30761759 ↗Structural, biochemical and biophysical characterization of recombinant human fumarate hydratase.Ajalla Aleixo MA et al. · 2019Structural, biochemical, and biophysical characterization of recombinant human fumarate hydratase solved at 1.8 Å resolution. The paper describes the HsFH domains (Domain 1: residues 49-188, Domain 2: 189-439, Domain 3: 440-510) but does not study or mention c.151C>T or any specific clinical variants.Does not name this variant
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PMID 20301430 ↗FH Tumor Predisposition Syndrome.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 24319509 ↗Canadian guideline on genetic screening for hereditary renal cell cancers.Reaume MN et al. · 2013No paper-specific finding is recorded.
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PMID 25004247 ↗Germline FH mutations presenting with pheochromocytoma.Clark GR et al. · 2014Identified two FH germline missense mutations (p.Glu53Lys and p.Cys434Tyr) in patients with pheochromocytoma. Both were shown to be catalytically inactive by functional assay. NM_000143.4:c.151C>T was not among the variants reported.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. Provides criteria for referring patients for genetic counseling. No variant-specific data are included.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
4 / 1,613,958 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
4 Likely pathogenic · 1 Uncertain significance · 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/649446/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/1-241680598-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr1-241517298-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/1-241517298-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000143.4%3Ac.151C…
- OncoKB ↗www.oncokb.org/gene/FH/R51W
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=135012036
- 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
This variant is present in gnomAD v4.1 (AF= 2.47838e-06; MAF= 0.00025%, 4/1613958 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.19602e-05; MAF= 0.00220%, 2/91074 alleles, homozygotes = 0); grpmax FAF= 3.65e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95893e-06; MAF= 0.00080%, 2/251290 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 6.53339e-05; MAF= 0.00653%, 2/30612 alleles, homozygotes = 0); grpmax FAF= 1.082e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely pathogenic (4 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Pathogenic (1 clinical laboratory). (ClinVarID = 649446)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.799. BayesDel score = 0.446505.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. FH, an enzyme that converts fumarate to malate in the TCA cycle, is infrequently altered in cancer.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV63818256, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.