NM_000126.3(ETFA):c.2T>C (p.Met1Thr) AND Glutaric aciduria, type 2

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: May 9, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000324694.3

Allele description [Variation Report for NM_000126.3(ETFA):c.2T>C (p.Met1Thr)]

NM_000126.3(ETFA):c.2T>C (p.Met1Thr)

Gene:
ETFA:electron transfer flavoprotein subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q24.3
Genomic location:
Preferred name:
NM_000126.3(ETFA):c.2T>C (p.Met1Thr)
Other names:
p.M1T:ATG>ACG
HGVS:
  • NC_000015.10:g.76311387A>G
  • NG_007077.2:g.5083T>C
  • NM_000126.3:c.2T>C
  • NP_000117.1:p.Met1Thr
  • NC_000015.9:g.76603728A>G
Protein change:
M1T
Links:
dbSNP: rs727503918
NCBI 1000 Genomes Browser:
rs727503918
Molecular consequence:
  • NM_000126.3:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000331585EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Jan 17, 2014)
germlineclinical testing

Citation Link,

SCV000815047Invitaecriteria provided, single submitter
Uncertain significance
(May 9, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients.

Freneaux E, Sheffield VC, Molin L, Shires A, Rhead WJ.

J Clin Invest. 1992 Nov;90(5):1679-86.

PubMed [citation]
PMID:
1430199
PMCID:
PMC443224

Expression and characterization of two pathogenic mutations in human electron transfer flavoprotein.

Salazar D, Zhang L, deGala GD, Frerman FE.

J Biol Chem. 1997 Oct 17;272(42):26425-33.

PubMed [citation]
PMID:
9334218
See all PubMed Citations (3)

Details of each submission

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000331585.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV000815047.1

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

Description

This sequence change affects the initiator methionine of the ETFA mRNA. The next in-frame methionine is located at codon 261. This variant is present in population databases (rs727503918, ExAC 0.02%). This variant has not been reported in the literature in individuals with ETFA-related disease. ClinVar contains an entry for this variant (Variation ID: 167039). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid(s) is currently unknown. The observation of one or more missense substitutions between codon 1 and codon 261 (p.Gly116Arg and p.Arg122Lys) in affected individuals suggests that this region may be a clinically significant (PMID: 1430199, 9334218, 16510302). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 17, 2019

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