NM_004453.3(ETFDH):c.488-9T>C AND Glutaric aciduria, type 2

Clinical significance:Uncertain significance (Last evaluated: Nov 9, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_004453.3(ETFDH):c.488-9T>C]


ETFDH:electron transfer flavoprotein dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000004.12:g.158685092T>C
  • NG_007078.2:g.17751T>C
  • NM_004453.3:c.488-9T>C
  • NC_000004.11:g.159606244T>C
dbSNP: rs1554031705
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_004453.3:c.488-9T>C - intron variant - [Sequence Ontology: SO:0001627]


Glutaric aciduria, type 2 (MADD)
GA II; GLUTARIC ACIDURIA II; Multiple Acyl Coenzyme A Dehydrogenase Deficiency
MedGen: C0268596; Orphanet: 26791; OMIM: 231680

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000631960Invitaecriteria provided, single submitter
Uncertain significance
(Nov 9, 2017)
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



Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations.

Wen B, Dai T, Li W, Zhao Y, Liu S, Zhang C, Li H, Wu J, Li D, Yan C.

J Neurol Neurosurg Psychiatry. 2010 Feb;81(2):231-6. doi: 10.1136/jnnp.2009.176404. Epub 2009 Sep 15.

PubMed [citation]

Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency.

Xi J, Wen B, Lin J, Zhu W, Luo S, Zhao C, Li D, Lin P, Lu J, Yan C.

J Inherit Metab Dis. 2014 May;37(3):399-404. doi: 10.1007/s10545-013-9671-6. Epub 2013 Dec 20.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000631960.2

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


This sequence change falls in intron 4 of the ETFDH gene. It does not directly change the encoded amino acid sequence of the ETFDH protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in at least one individual affected with ETFDH-related disorders (PMID: 19758981, 24357026). This variant is also know as IVS4-9T>C in the literature. Experimental studies on cDNA from muscle tissue from a patient affected with riboflavin-responsive lipid-storage myopathy showed that this variant led to a truncated transcript. However, Western blot analysis only showed moderate reduction in protein expression (PMID: 19758981). Additional data quantifying the ratio of truncated transcripts relative to the wild type transcript are needed to ascertain the functional impact of this variant. In summary, this variant has been reported in at least one affected individual and shown to interfere with RNA splicing and protein expression. However, additional experimental or genetic data are needed to ascertain the functional and clinical significance of this variant. For these reasons, this change has been classified as a Variant of Uncertain Significance.

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

Last Updated: Mar 30, 2019

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