NM_000018.4(ACADVL):c.890_892AGA[2] (p.Lys299del) AND Very long chain acyl-CoA dehydrogenase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (5 submissions)
Last evaluated:: Nov 1, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000001694.10

Allele description

NM_000018.4(ACADVL):c.890_892AGA[2] (p.Lys299del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.890_892AGA[2] (p.Lys299del)

HGVS:

NC_000017.11:g.7222678_7222680AGA[2]
NG_007975.1:g.7845_7847AGA[2]
NG_008391.2:g.2365_2367TCT[2]
NM_000018.4:c.890_892AGA[2]MANE SELECT
NM_001033859.2:c.824_826AGA[2]
NM_001270447.1:c.959_961AGA[2]
NP_000009.1:p.Lys299del
NP_000009.1:p.Lys299del
NP_001029031.1:p.Lys277del
NP_001257376.1:p.Lys322del
NP_001257377.1:p.Lys223del
NC_000017.10:g.7125997_7125999AGA[2]
NM_000018.2:c.896_898delAGA
NM_000018.3:c.896_898del
NM_001270448.1:c.662_664AGA[2]
NM_001270448.1:c.668_670delAGA
p.Lys223del

Protein change:

K223del

Links:

OMIM: 609575.0007; dbSNP: rs387906252

NCBI 1000 Genomes Browser:

rs387906252

Molecular consequence:

NM_000018.4:c.890_892AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001033859.2:c.824_826AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001270447.1:c.959_961AGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Very long chain acyl-CoA dehydrogenase deficiency (VLCAD)
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
SCV000021850	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 1996)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000220685	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Sep 10, 2014)	unknown	literature only	PubMed (1) [See all records that cite this PMID] Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000654974	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28755359, 8554073, 23480858, 28492532
SCV001364909	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 1, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8554073, 25741868
SCV001522469	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 9, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

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

Citations

PubMed

Four Years' Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers.

Merinero B, Alcaide P, Martín-Hernández E, Morais A, García-Silva MT, Quijada-Fraile P, Pedrón-Giner C, Dulin E, Yahyaoui R, Egea JM, Belanger-Quintana A, Blasco-Alonso J, Fernandez Ruano ML, Besga B, Ferrer-López I, Leal F, Ugarte M, Ruiz-Sala P, Pérez B, Pérez-Cerdá C.

JIMD Rep. 2018;39:63-74. doi: 10.1007/8904_2017_40. Epub 2017 Jul 29.

PubMed [citation]

PMID:: 28755359
PMCID:: PMC5953901

Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency.

Schiff M, Mohsen AW, Karunanidhi A, McCracken E, Yeasted R, Vockley J.

Mol Genet Metab. 2013 May;109(1):21-7. doi: 10.1016/j.ymgme.2013.02.002. Epub 2013 Feb 13.

PubMed [citation]

PMID:: 23480858
PMCID:: PMC3628282

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000021850.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an infant with VLCAD deficiency (201475), Souri et al. (1996) found deletion of nucleotides 895-897 in the ACADVL gene, resulting in deletion of lys299 (K299X).

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

From Counsyl, SCV000220685.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Invitae, SCV000654974.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change deletes 3 nucleotides from exon 10 of the ACADVL mRNA (c.896_898delAGA). This leads to the deletion of 1 amino acid residue in the ACADVL protein (p.Lys299del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs761162357, ExAC 0.01%). This variant has been reported as heterozygous in individuals with suspected VLCAD deficiency (PMID: 23480858, 8554073, 28755359). ClinVar contains an entry for this variant (Variation ID: 92292). Experimental studies have shown that this deletion affects protein stability and activity in vitro (PMID: 8554073). 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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001364909.2

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

Description

The NM_000018.3:c.896_898delAGA (NP_000009.1:p.Lys299del) [GRCH38: NC_000017.11:g.7222684_7222686delAGA] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 8554073. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3

#	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

From Baylor Genetics, SCV001522469.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

Last Updated: May 23, 2021

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