NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Oct 21, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001239627.1

Allele description [Variation Report for NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer)]

NM_000182.5(HADHA):c.1967del (p.Ile655_Leu656insTer)

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.1967del (p.Ile655_Leu656insTer)
HGVS:
  • NC_000002.12:g.26192346del
  • NG_007121.1:g.57278del
  • NM_000182.5:c.1967delMANE SELECT
  • NP_000173.2:p.Ile655_Leu656insTer
  • LRG_747t1:c.1967del
  • LRG_747p1:p.Ile655_Leu656insTer
  • NC_000002.11:g.26415215del
  • NM_000182.4:c.1967del
  • NM_000182.4:c.1967delT
Links:
dbSNP: rs779113356
NCBI 1000 Genomes Browser:
rs779113356
Molecular consequence:
  • NM_000182.5:c.1967del - nonsense - [Sequence Ontology: SO:0001587]

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
SCV001412513Invitaecriteria provided, single submitter
Pathogenic
(Oct 21, 2019)
germlineclinical testing

PubMed (3)
[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

A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.

Ibdah JA, Bennett MJ, Rinaldo P, Zhao Y, Gibson B, Sims HF, Strauss AW.

N Engl J Med. 1999 Jun 3;340(22):1723-31.

PubMed [citation]
PMID:
10352164

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, Acquaviva C, Vianey-Saban C, de Lonlay P, de Baulny HO, Guffon N, Dobbelaere D, Feillet F, Labarthe F, Lamireau D, Cano A, de Villemeur TB, Munnich A, Saudubray JM, Rabier D, Rigal O, Brivet M.

Mol Genet Metab. 2011 Aug;103(4):341-8. doi: 10.1016/j.ymgme.2011.04.006. Epub 2011 Apr 19.

PubMed [citation]
PMID:
21549624
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001412513.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu656*) in the HADHA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs779113356, ExAC 0.001%). This variant has been observed in individuals affected with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency or deficiency of mitochondrial trifunctional protein (PMID: 10352164, 21549624). This variant is also known as Leu620Ter in the literature. ClinVar contains an entry for this variant (Variation ID: 188712). 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 27, 2021

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