NM_000018.4(ACADVL):c.686_726del (p.Arg229fs) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 10, 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:: RCV003602475.1

Allele description [Variation Report for NM_000018.4(ACADVL):c.686_726del (p.Arg229fs)]

NM_000018.4(ACADVL):c.686_726del (p.Arg229fs)

Gene:

ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.686_726del (p.Arg229fs)

HGVS:

NC_000017.11:g.7222015_7222055del
NG_007975.1:g.7182_7222del
NG_008391.2:g.2998_3038del
NG_008391.3:g.2997_3037del
NM_000018.4:c.686_726delMANE SELECT
NM_001033859.3:c.620_660del
NM_001270447.2:c.755_795del
NM_001270448.2:c.458_498del
NP_000009.1:p.Arg229fs
NP_001029031.1:p.Arg207fs
NP_001257376.1:p.Arg252fs
NP_001257377.1:p.Arg153fs
NC_000017.10:g.7125332_7125372del
NC_000017.10:g.7125334_7125374del

Protein change:

R153fs

Molecular consequence:

NM_000018.4:c.686_726del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001033859.3:c.620_660del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270447.2:c.755_795del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270448.2:c.458_498del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004453528	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9973285, 11590124, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004453528

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 10, 2023)

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

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N.

Am J Hum Genet. 1999 Feb;64(2):479-94.

PubMed [citation]

PMID:: 9973285
PMCID:: PMC1377757

Gestational, pathologic and biochemical differences between very long-chain acyl-CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in the mouse.

Cox KB, Hamm DA, Millington DS, Matern D, Vockley J, Rinaldo P, Pinkert CA, Rhead WJ, Lindsey JR, Wood PA.

Hum Mol Genet. 2001 Sep 15;10(19):2069-77.

PubMed [citation]

PMID:: 11590124

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004453528.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. This variant is present in population databases (rs768471244, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg229Profs*10) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124).

#	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: Feb 28, 2024

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