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

Clinical significance:Pathogenic (Last evaluated: Aug 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001041924.2

Allele description [Variation Report for NM_000182.5(HADHA):c.1793_1794del (p.His598fs)]

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

Genes:
GAREM2:GRB2 associated regulator of MAPK1 subtype 2 [Gene - OMIM - HGNC]
HADHA:hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_000182.5(HADHA):c.1793_1794del (p.His598fs)
HGVS:
  • NC_000002.12:g.26193668_26193669del
  • NG_007121.1:g.55952_55953del
  • NM_000182.5:c.1793_1794delMANE SELECT
  • NP_000173.2:p.His598fs
  • LRG_747t1:c.1793_1794del
  • LRG_747p1:p.His598fs
  • NC_000002.11:g.26416537_26416538del
  • NM_000182.4:c.1793_1794del
  • NM_000182.4:c.1793_1794delAT
  • NM_000182.5:c.1793_1794delATMANE SELECT
Protein change:
H598fs
Links:
dbSNP: rs769580842
NCBI 1000 Genomes Browser:
rs769580842
Molecular consequence:
  • NM_000182.5:c.1793_1794del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Mitochondrial trifunctional protein deficiency (MTPD)
Synonyms:
Trifunctional protein deficiency with myopathy and neuropathy; Trifunctional protein deficiency type 1; TFP deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012172; MedGen: C1969443; Orphanet: 746; OMIM: 609015
Name:
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Synonyms:
Deficiency of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase
Identifiers:
MONDO: MONDO:0012173; MedGen: C3711645; Orphanet: 5; OMIM: 609016

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001205577Invitaecriteria provided, single submitter
Pathogenic
(Aug 27, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies.

Hintz SR, Matern D, Strauss A, Bennett MJ, Hoyme HE, Schelley S, Kobori J, Colby C, Lehman NL, Enns GM.

Mol Genet Metab. 2002 Feb;75(2):120-7.

PubMed [citation]
PMID:
11855930

Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.

Brackett JC, Sims HF, Rinaldo P, Shapiro S, Powell CK, Bennett MJ, Strauss AW.

J Clin Invest. 1995 May;95(5):2076-82.

PubMed [citation]
PMID:
7738175
PMCID:
PMC295799
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001205577.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

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 product. This variant is present in population databases (rs769580842, ExAC 0.01%). This variant has been observed in an individual affected with mitochondrial trifunctional protein deficiency (PMID: 11855930). ClinVar contains an entry for this variant (Variation ID: 188962). Loss-of-function variants in HADHA are known to be pathogenic (PMID: 7738175, 21103935, 21549624, 22459206). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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