NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 25, 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:: RCV004019829.1

Allele description [Variation Report for NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)]

NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)

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.1591C>T (p.Arg531Trp)

HGVS:

NC_000017.11:g.7224379C>T
NG_007975.1:g.9546C>T
NG_008391.2:g.672G>A
NG_033038.1:g.15166G>A
NM_000018.4:c.1591C>TMANE SELECT
NM_001033859.3:c.1525C>T
NM_001270447.2:c.1660C>T
NM_001270448.2:c.1363C>T
NP_000009.1:p.Arg531Trp
NP_000009.1:p.Arg531Trp
NP_001029031.1:p.Arg509Trp
NP_001257376.1:p.Arg554Trp
NP_001257377.1:p.Arg455Trp
NP_001257377.1:p.Arg455Trp
NC_000017.10:g.7127698C>T
NM_000018.2:c.1591C>T
NM_000018.3:c.1591C>T
NM_001270448.1:c.1363C>T

Protein change:

R455W

Links:

dbSNP: rs146379816

NCBI 1000 Genomes Browser:

rs146379816

Molecular consequence:

NM_000018.4:c.1591C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1525C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1660C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.1363C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004915369	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Oct 25, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9599005, 18227065, 21932095, 31031081, 35281659 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004915369

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Oct 25, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Very-long-chain acyl-CoA dehydrogenase subunit assembles to the dimer form on mitochondrial inner membrane.

Souri M, Aoyama T, Hoganson G, Hashimoto T.

FEBS Lett. 1998 Apr 17;426(2):187-90.

PubMed [citation]

PMID:: 9599005

Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase.

McAndrew RP, Wang Y, Mohsen AW, He M, Vockley J, Kim JJ.

J Biol Chem. 2008 Apr 4;283(14):9435-43. doi: 10.1074/jbc.M709135200. Epub 2008 Jan 28.

PubMed [citation]

PMID:: 18227065
PMCID:: PMC2431035

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV004915369.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The c.1591C>T (p.R531W) alteration is located in exon 16 (coding exon 16) of the ACADVL gene. This alteration results from a C to T substitution at nucleotide position 1591, causing the arginine (R) at amino acid position 531 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.044% (123/281458) total alleles studied. The highest observed frequency was 0.076% (98/128338) of European (non-Finnish) alleles. This variant has been detected in conjunction with multiple ACADVL variants in individuals with clinical and biochemical features of VLCAD deficiency (Hoffmann, 2012; Rovelli, 2019; Olsson, 2022). This amino acid position is not well conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: Nov 3, 2024

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