NM_000018.4(ACADVL):c.1592G>A (p.Arg531Gln) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 24, 2022
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:: RCV001944804.5

Allele description [Variation Report for NM_000018.4(ACADVL):c.1592G>A (p.Arg531Gln)]

NM_000018.4(ACADVL):c.1592G>A (p.Arg531Gln)

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.1592G>A (p.Arg531Gln)

HGVS:

NC_000017.11:g.7224380G>A
NG_007975.1:g.9547G>A
NG_008391.2:g.671C>T
NG_033038.1:g.15165C>T
NM_000018.4:c.1592G>AMANE SELECT
NM_001033859.3:c.1526G>A
NM_001270447.2:c.1661G>A
NM_001270448.2:c.1364G>A
NP_000009.1:p.Arg531Gln
NP_001029031.1:p.Arg509Gln
NP_001257376.1:p.Arg554Gln
NP_001257377.1:p.Arg455Gln
NC_000017.10:g.7127699G>A

Protein change:

R455Q

Links:

dbSNP: rs772763960

NCBI 1000 Genomes Browser:

rs772763960

Molecular consequence:

NM_000018.4:c.1592G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1526G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1661G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.1364G>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

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CEACAM7 [Chlorocebus sabaeus]
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002131664	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 24, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21932095, 31031081, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002131664

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 24, 2022)

germline

clinical testing

PubMed (3)
[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

VLCAD enzyme activity determinations in newborns identified by screening: a valuable tool for risk assessment.

Hoffmann L, Haussmann U, Mueller M, Spiekerkoetter U.

J Inherit Metab Dis. 2012 Mar;35(2):269-77. doi: 10.1007/s10545-011-9391-8. Epub 2011 Sep 20.

PubMed [citation]

PMID:: 21932095

Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency.

Rovelli V, Manzoni F, Viau K, Pasquali M, Longo N.

Mol Genet Metab. 2019 May;127(1):64-73. doi: 10.1016/j.ymgme.2019.04.001. Epub 2019 Apr 16.

PubMed [citation]

PMID:: 31031081

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002131664.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 531 of the ACADVL protein (p.Arg531Gln). This variant is present in population databases (rs772763960, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1366698). 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. This variant disrupts the p.Arg531 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21932095, 31031081; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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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