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NM_000182.5(HADHA):c.1793_1794del (p.His598fs)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
4 (Most recent: Nov 16, 2021)
Last evaluated:
Oct 17, 2021
Accession:
VCV000188962.9
Variation ID:
188962
Description:
2bp deletion
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NM_000182.5(HADHA):c.1793_1794del (p.His598fs)

Allele ID
186666
Variant type
Deletion
Variant length
2 bp
Cytogenetic location
2p23.3
Genomic location
2: 26193668-26193669 (GRCh38) GRCh38 UCSC
2: 26416537-26416538 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000002.11:g.26416537_26416538del
NC_000002.12:g.26193668_26193669del
NG_007121.1:g.55952_55953del
... more HGVS
Protein change
H598fs
Other names
-
Canonical SPDI
NC_000002.12:26193667:AT:
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00003
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Links
ClinGen: CA199104
dbSNP: rs769580842
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter Sep 10, 2014 RCV000169337.6
Pathogenic 1 criteria provided, single submitter Aug 27, 2020 RCV001041924.2
Pathogenic 1 criteria provided, single submitter Oct 17, 2021 RCV001778769.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GAREM2 - - GRCh38
GRCh37
1 257
HADHA - - GRCh38
GRCh37
217 476

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Sep 10, 2014)
criteria provided, single submitter
Method: literature only
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000220683.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (3)
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
Mitochondrial trifunctional protein deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV001205577.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change creates a premature translational stop signal (p.His598Argfs*33) in the HADHA gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Oct 17, 2021)
criteria provided, single submitter
Method: clinical testing
Mitochondrial trifunctional protein deficiency
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917471.2
Submitted: (Nov 16, 2021)
Evidence details
Publications
PubMed (7)
Comment:
Variant summary: HADHA c.1793_1794delAT (p.His598ArgfsX33) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Deficiency of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase
Allele origin: germline
Natera, Inc.
Accession: SCV001458396.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The role of exome sequencing in newborn screening for inborn errors of metabolism. Adhikari AN Nature medicine 2020 PMID: 32778825
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. Hou YC Proceedings of the National Academy of Sciences of the United States of America 2020 PMID: 31980526
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. Capalbo A PLoS genetics 2019 PMID: 31589614
Clinical and genetic characteristics of patients with fatty acid oxidation disorders identified by newborn screening. Kang E BMC pediatrics 2018 PMID: 29519241
Observations regarding retinopathy in mitochondrial trifunctional protein deficiencies. Fletcher AL Molecular genetics and metabolism 2012 PMID: 22459206
Comprehensive cDNA study and quantitative analysis of mutant HADHA and HADHB transcripts in a French cohort of 52 patients with mitochondrial trifunctional protein deficiency. Boutron A Molecular genetics and metabolism 2011 PMID: 21549624
Urgent metabolic service improves survival in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency detected by symptomatic identification and pilot newborn screening. Sykut-Cegielska J Journal of inherited metabolic disease 2011 PMID: 21103935
A case of mitochondrial trifunctional protein deficiency diagnosed by acylcarnitine profile and DNA analysis in a dried blood spot of a 4-day-old boy. Lee JE Journal of inherited metabolic disease 2003 PMID: 12971428
Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations. Spiekerkoetter U Human mutation 2002 PMID: 12442268
Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies. Hintz SR Molecular genetics and metabolism 2002 PMID: 11855930
Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. Brackett JC The Journal of clinical investigation 1995 PMID: 7738175

Text-mined citations for rs769580842...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021