NM_000126.3(ETFA):c.20C>T (p.Pro7Leu) AND Glutaric aciduria, type 2

Clinical significance:Uncertain significance (Last evaluated: Jun 25, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000702647.1

Allele description [Variation Report for NM_000126.3(ETFA):c.20C>T (p.Pro7Leu)]

NM_000126.3(ETFA):c.20C>T (p.Pro7Leu)

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.20C>T (p.Pro7Leu)
HGVS:
  • NC_000015.10:g.76311369G>A
  • NG_007077.2:g.5101C>T
  • NM_000126.3:c.20C>T
  • NP_000117.1:p.Pro7Leu
  • NC_000015.9:g.76603710G>A
Protein change:
P7L
Molecular consequence:
  • NM_000126.3:c.20C>T - 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
SCV000831509Invitaecriteria provided, single submitter
Uncertain significance
(Jun 25, 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, SCV000831509.1

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

Description

This sequence change replaces proline with leucine at codon 7 of the ETFA protein (p.Pro7Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs557160401, ExAC 1.5%). This variant has not been reported in the literature in individuals with ETFA-related disease. 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 tolerated, 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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