NM_004453.3(ETFDH):c.679C>A (p.Pro227Thr) AND Glutaric aciduria, type 2

Clinical significance:Uncertain significance (Last evaluated: Jul 12, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000558221.1

Allele description [Variation Report for NM_004453.3(ETFDH):c.679C>A (p.Pro227Thr)]

NM_004453.3(ETFDH):c.679C>A (p.Pro227Thr)

Gene:
ETFDH:electron transfer flavoprotein dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q32.1
Genomic location:
Preferred name:
NM_004453.3(ETFDH):c.679C>A (p.Pro227Thr)
HGVS:
  • NC_000004.12:g.158690420C>A
  • NG_007078.2:g.23079C>A
  • NM_004453.3:c.679C>A
  • NP_004444.2:p.Pro227Thr
  • NC_000004.11:g.159611572C>A
Protein change:
P227T
Links:
dbSNP: rs141407224
NCBI 1000 Genomes Browser:
rs141407224
Molecular consequence:
  • NM_004453.3:c.679C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000631961Invitaecriteria provided, single submitter
Uncertain significance
(Jul 12, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000631961.1

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

Description

This sequence change replaces proline with threonine at codon 227 of the ETFDH protein (p.Pro227Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs141407224, ExAC 0.01%). This variant has been reported in an individual affected with glutaric aciduria type II (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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: Mar 30, 2019

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