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NM_000182.5(HADHA):c.180+3A>G

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 13, 2020
Accession:
VCV000008731.9
Variation ID:
8731
Description:
single nucleotide variant
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NM_000182.5(HADHA):c.180+3A>G

Allele ID
23770
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2p23.3
Genomic location
2: 26238931 (GRCh38) GRCh38 UCSC
2: 26461799 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_747t1:c.180+3A>G
NC_000002.11:g.26461799T>C
NC_000002.12:g.26238931T>C
... more HGVS
Protein change
-
Other names
IVS3DS, A-G, +3
Canonical SPDI
NC_000002.12:26238930:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00005
Exome Aggregation Consortium (ExAC) 0.00009
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
OMIM: 600890.0004
dbSNP: rs781222705
ClinGen: CA213113
VarSome
Comment on variant
NCBI staff reviewed the sequence information reported in PubMed 7738175 Fig. 5 to determine the location of this allele on the current reference sequence.
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 2 criteria provided, multiple submitters, no conflicts Jul 1, 2016 RCV000185934.3
Pathogenic 2 criteria provided, multiple submitters, no conflicts Sep 13, 2020 RCV000763079.4
Pathogenic 3 criteria provided, single submitter Jul 2, 2020 RCV000984272.3
Pathogenic 1 no assertion criteria provided May 1, 1995 RCV000009270.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
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
Pathogenic
(Oct 13, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000228808.5
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Mitochondrial trifunctional protein deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000893602.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Jul 02, 2020)
criteria provided, single submitter
Method: clinical testing
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001426898.1
Submitted: (Aug 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: HADHA c.180+3A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more)
Pathogenic
(Jul 01, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000238890.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The c.180+3 A>G splice site variant in the HADHA gene has been previously reported in association with mitochondrial trifunctional protein deficiency (Brackett et al., 1995). … (more)
Pathogenic
(Sep 13, 2020)
criteria provided, single submitter
Method: clinical testing
Mitochondrial trifunctional protein deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV000945227.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change falls in intron 3 of the HADHA gene. It does not directly change the encoded amino acid sequence of the HADHA protein, … (more)
Likely pathogenic
(Sep 11, 2015)
no assertion criteria provided
Method: clinical testing
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Allele origin: unknown
Counsyl
Accession: SCV001132411.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (3)
Pathogenic
(May 01, 1995)
no assertion criteria provided
Method: literature only
MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY
Allele origin: germline
OMIM
Accession: SCV000029488.4
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)
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: SCV001462522.1
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
Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional Protein Disorders: Long-Term Follow-up of 21 Cases. Boese EA Ophthalmology 2016 PMID: 27491397
Mitochondrial trifunctional protein deficiency in human cultured fibroblasts: effects of bezafibrate. Djouadi F Journal of inherited metabolic disease 2016 PMID: 26109258
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. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset rhabdomyolysis. Liewluck T Muscle & nerve 2013 PMID: 23868323
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Buratti E Nucleic acids research 2007 PMID: 17576681
Statistical features of human exons and their flanking regions. Zhang MQ Human molecular genetics 1998 PMID: 9536098
Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. Brackett JC The Journal of clinical investigation 1995 PMID: 7738175
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=HADHA - - - -

Text-mined citations for rs781222705...

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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 Aug 27, 2021