NM_001985.2(ETFB):c.227G>A (p.Arg76His) AND Glutaric aciduria, type 2

Clinical significance:Uncertain significance (Last evaluated: Jan 17, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000548291.2

Allele description [Variation Report for NM_001985.2(ETFB):c.227G>A (p.Arg76His)]

NM_001985.2(ETFB):c.227G>A (p.Arg76His)

Gene:
ETFB:electron transfer flavoprotein subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.41
Genomic location:
Preferred name:
NM_001985.2(ETFB):c.227G>A (p.Arg76His)
Other names:
p.R76H:CGT>CAT
HGVS:
  • NC_000019.10:g.51353280C>T
  • NG_007115.1:g.18139G>A
  • NM_001985.2:c.227G>A
  • NP_001976.1:p.Arg76His
  • NC_000019.9:g.51856534C>T
Protein change:
R76H
Links:
dbSNP: rs148567433
NCBI 1000 Genomes Browser:
rs148567433
Molecular consequence:
  • NM_001985.2:c.227G>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
SCV000631949Invitaecriteria provided, single submitter
Uncertain significance
(Jan 17, 2018)
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, SCV000631949.2

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

Description

This sequence change replaces arginine with histidine at codon 76 of the ETFB protein (p.Arg76His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs148567433, ExAC 0.03%) but has not been reported in the literature in individuals with a ETFB-related disease. ClinVar contains an entry for this variant (Variation ID: 203702). 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. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. 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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