NM_000018.3(ACADVL):c.538G>A (p.Ala180Thr) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Jun 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000152735.7

Allele description [Variation Report for NM_000018.3(ACADVL):c.538G>A (p.Ala180Thr)]

NM_000018.3(ACADVL):c.538G>A (p.Ala180Thr)

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.3(ACADVL):c.538G>A (p.Ala180Thr)
Other names:
p.A180T:GCC>ACC
HGVS:
  • NC_000017.11:g.7221598G>A
  • NG_007975.1:g.6765G>A
  • NM_000018.3:c.538G>A
  • NM_001033859.2:c.472G>A
  • NM_001270448.1:c.310G>A
  • NP_000009.1:p.Ala180Thr
  • NP_001029031.1:p.Ala158Thr
  • NP_001257377.1:p.Ala104Thr
  • NC_000017.10:g.7124917G>A
  • NM_000018.2:c.538G>A
  • NM_001033859.1:c.472G>A
Protein change:
A104T
Links:
dbSNP: rs727503791
NCBI 1000 Genomes Browser:
rs727503791
Molecular consequence:
  • NM_000018.3:c.538G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000202122EGL Genetic Diagnostics,Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Jun 23, 2017)
germlineclinical testing

Citation Link,

SCV000238635GeneDxcriteria provided, single submitter
Pathogenic
(Mar 26, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics,Eurofins Clinical Diagnostics, SCV000202122.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000238635.12

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The A180T missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It has been seen previously at GeneDx in multiple patients referred for analysis of the ACADVL gene. One such patient also harbored a previously reported disease-associated ACADVL missense mutation. A180T is a nonconservative amino acid change in that a hydrophobic amino acid, Alanine, is replaced by a hydrophilic amino acid, Threonine. This missense change occurs at a highly conserved position in the ACADVL protein across species and in other acyl-CoA dehydrogenases. Multiple missense mutations at nearby positions (V174M, L178P, G179W, G185W, G185S, I189T) have been reported in association with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, and multiple in-silico analysis programs predict that A180T is damaging to the ACADVL protein. Therefore, we interpret A180T to be a pathogenic mutation.The variant is found in ACADVL panel(s).

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

Last Updated: Mar 30, 2019

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