NM_000018.4(ACADVL):c.490G>A (p.Val164Met) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 24, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003497768.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.490G>A (p.Val164Met)]

NM_000018.4(ACADVL):c.490G>A (p.Val164Met)

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.490G>A (p.Val164Met)

HGVS:

NC_000017.11:g.7221550G>A
NG_007975.1:g.6717G>A
NG_008391.2:g.3501C>T
NG_008391.3:g.3500C>T
NM_000018.4:c.490G>AMANE SELECT
NM_001033859.3:c.424G>A
NM_001270447.2:c.559G>A
NM_001270448.2:c.262G>A
NP_000009.1:p.Val164Met
NP_001029031.1:p.Val142Met
NP_001257376.1:p.Val187Met
NP_001257377.1:p.Val88Met
NC_000017.10:g.7124869G>A

Protein change:

V142M

Molecular consequence:

NM_000018.4:c.490G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.424G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.559G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.262G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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AP-4 complex subunit sigma-1 isoform 1 [Homo sapiens]
AP-4 complex subunit sigma-1 isoform 1 [Homo sapiens]
gi|21361394|ref|NP_009008.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004311665	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 24, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23169530, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004311665

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 24, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel mutations in the gene encoding very long-chain acyl-CoA dehydrogenase identified in patients with partial carnitine palmitoyltransferase II deficiency.

Isackson PJ, Sutton KA, Hostetler KY, Vladutiu GD.

Muscle Nerve. 2013 Feb;47(2):224-9. doi: 10.1002/mus.23498. Epub 2012 Nov 21.

PubMed [citation]

PMID:: 23169530

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004311665.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val164 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23169530; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADVL protein function. This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 164 of the ACADVL protein (p.Val164Met).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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