NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Nov 27, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000537897.6

Allele description [Variation Report for NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met)]

NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met)

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_000018.4(ACADVL):c.1239A>G (p.Ile413Met)
HGVS:
  • NC_000017.11:g.7223700A>G
  • NG_007975.1:g.8867A>G
  • NG_008391.2:g.1351T>C
  • NG_033038.1:g.15845T>C
  • NM_000018.4:c.1239A>GMANE SELECT
  • NM_001033859.2:c.1173A>G
  • NM_001270447.1:c.1308A>G
  • NM_001270448.1:c.1011A>G
  • NP_000009.1:p.Ile413Met
  • NP_001029031.1:p.Ile391Met
  • NP_001257376.1:p.Ile436Met
  • NP_001257377.1:p.Ile337Met
  • NC_000017.10:g.7127019A>G
  • NM_000018.3:c.1239A>G
  • p.Ile413Met
Protein change:
I337M
Links:
dbSNP: rs143172658
NCBI 1000 Genomes Browser:
rs143172658
Molecular consequence:
  • NM_000018.4:c.1239A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.2:c.1173A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.1:c.1308A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.1:c.1011A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (VLCAD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000654922Invitaecriteria provided, single submitter
Likely benign
(Nov 27, 2020)
germlineclinical testing

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

SCV001288092Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

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

Citation Link,

SCV001365208Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Uncertain significance
(Nov 1, 2019)
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. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

A heterozygous missense mutation in adolescent-onset very long-chain acyl-CoA dehydrogenase deficiency with exercise-induced rhabdomyolysis.

Hisahara S, Matsushita T, Furuyama H, Tajima G, Shigematsu Y, Imai T, Shimohama S.

Tohoku J Exp Med. 2015 Apr;235(4):305-10. doi: 10.1620/tjem.235.305.

PubMed [citation]
PMID:
25843429
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000654922.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001288092.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365208.2

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

Description

The NM_000018.3:c.1239A>G (NP_000009.1:p.Ile413Met) [GRCH38: NC_000017.11:g.7223700A>G] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: BP4

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

Last Updated: Jun 14, 2021

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