NM_000018.4(ACADVL):c.1838G>C (p.Arg613Pro) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 17, 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:: RCV003086036.3

Allele description [Variation Report for NM_000018.4(ACADVL):c.1838G>C (p.Arg613Pro)]

NM_000018.4(ACADVL):c.1838G>C (p.Arg613Pro)

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.1838G>C (p.Arg613Pro)

HGVS:

NC_000017.11:g.7224967G>C
NG_007975.1:g.10134G>C
NG_008391.3:g.83C>G
NG_033038.1:g.14578C>G
NG_135375.1:g.112G>C
NM_000018.4:c.1838G>CMANE SELECT
NM_001033859.3:c.1772G>C
NM_001270447.2:c.1907G>C
NM_001270448.2:c.1610G>C
NP_000009.1:p.Arg613Pro
NP_001029031.1:p.Arg591Pro
NP_001257376.1:p.Arg636Pro
NP_001257377.1:p.Arg537Pro
NC_000017.10:g.7128286G>C
NG_008391.2:g.84C>G

Protein change:

R537P

Molecular consequence:

NM_000018.4:c.1838G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1772G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1907G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.1610G>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003472240	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 7479827, 8554073, 10077518, 17374501, 17999356, 19327992, 35281659, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003472240

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2022)

germline

clinical testing

PubMed (8)
[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

Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.

Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF.

Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10496-500.

PubMed [citation]

PMID:: 7479827
PMCID:: PMC40638

Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: identification and characterization of mutant VLCAD cDNAs from four patients.

Souri M, Aoyama T, Orii K, Yamaguchi S, Hashimoto T.

Am J Hum Genet. 1996 Jan;58(1):97-106.

PubMed [citation]

PMID:: 8554073
PMCID:: PMC1914938

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003472240.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg613 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7479827, 8554073, 10077518, 17374501, 17999356, 19327992). 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 missense change has been observed in individual(s) with very long chain acyl-CoA dehydrogenase deficiency (PMID: 35281659). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 613 of the ACADVL protein (p.Arg613Pro).

#	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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