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NM_000018.4(ACADVL):c.538G>A (p.Ala180Thr)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(2);Pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Sep 30, 2021)
Last evaluated:
May 27, 2021
Accession:
VCV000166641.8
Variation ID:
166641
Description:
single nucleotide variant
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NM_000018.4(ACADVL):c.538G>A (p.Ala180Thr)

Allele ID
177029
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.1
Genomic location
17: 7221598 (GRCh38) GRCh38 UCSC
17: 7124917 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.7124917G>A
NM_001270448.1:c.310G>A NP_001257377.1:p.Ala104Thr missense
NC_000017.11:g.7221598G>A
... more HGVS
Protein change
A180T, A158T, A104T, A203T
Other names
p.A180T:GCC>ACC
Canonical SPDI
NC_000017.11:7221597:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA295584
dbSNP: rs727503791
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations May 27, 2021 RCV000152735.8
Conflicting interpretations of pathogenicity 4 criteria provided, conflicting interpretations Oct 21, 2020 RCV000675106.6
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ACADVL - - GRCh38
GRCh37
898 981

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 16, 2018)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: unknown
Counsyl
Accession: SCV000800653.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Jun 23, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000202122.7
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Likely pathogenic
(Nov 13, 2018)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602371.2
Submitted: (Aug 05, 2019)
Evidence details
Comment:
The ACADVL c.538G>A; p.Ala180Thr variant (rs727503791) is reported in the literature to be significantly enriched in patients with abnormal newborn screening results suggestive of VLCAD … (more)
Likely pathogenic
(Nov 01, 2019)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine
Accession: SCV001365220.2
Submitted: (Jul 13, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The NM_000018.3:c.538G>A (NP_000009.1:p.Ala180Thr) [GRCH38: NC_000017.11:g.7221598G>A] variant in ACADVL gene is interpretated to be Likely Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been … (more)
Uncertain significance
(Oct 21, 2020)
criteria provided, single submitter
Method: clinical testing
Very long chain acyl-CoA dehydrogenase deficiency
Allele origin: germline
Invitae
Accession: SCV001233673.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces alanine with threonine at codon 180 of the ACADVL protein (p.Ala180Thr). The alanine residue is highly conserved and there is a … (more)
Pathogenic
(May 27, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000238635.13
Submitted: (Sep 30, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The diagnostic challenge in very-long chain acyl-CoA dehydrogenase deficiency (VLCADD). Hesse J Journal of inherited metabolic disease 2018 PMID: 30194637
Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Miller MJ Molecular genetics and metabolism 2015 PMID: 26385305
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ACADVL - - - -

Text-mined citations for rs727503791...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021