NM_000018.4(ACADVL):c.1522C>T (p.Gln508Ter) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002308456.7

Allele description [Variation Report for NM_000018.4(ACADVL):c.1522C>T (p.Gln508Ter)]

NM_000018.4(ACADVL):c.1522C>T (p.Gln508Ter)

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.1522C>T (p.Gln508Ter)

HGVS:

NC_000017.11:g.7224233C>T
NG_007975.1:g.9400C>T
NG_008391.3:g.817G>A
NG_033038.1:g.15312G>A
NM_000018.4:c.1522C>TMANE SELECT
NM_001033859.3:c.1456C>T
NM_001270447.2:c.1591C>T
NM_001270448.2:c.1294C>T
NP_000009.1:p.Gln508Ter
NP_001029031.1:p.Gln486Ter
NP_001257376.1:p.Gln531Ter
NP_001257377.1:p.Gln432Ter
NC_000017.10:g.7127552C>T
NG_008391.2:g.818G>A

Protein change:

Q432*

Molecular consequence:

NM_000018.4:c.1522C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001033859.3:c.1456C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001270447.2:c.1591C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001270448.2:c.1294C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:: VLCAD deficiency
Identifiers:: MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

Recent activity

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Ndel1 nudE neurodevelopment protein 1-like 1 [Rattus norvegicus]
Ndel1 nudE neurodevelopment protein 1-like 1 [Rattus norvegicus]
Gene ID:170845

Gene
170845[uid] AND (alive[prop]) (1)
Gene
Erigeron epiroticus (0)
Nucleotide
PREDICTED: Mus musculus predicted gene, 30515 (Gm30515), transcript variant X7, ...
PREDICTED: Mus musculus predicted gene, 30515 (Gm30515), transcript variant X7, ncRNA
gi|1039742512|ref|XR_001780583.1|

Nucleotide
Homo sapiens bone morphogenetic protein 4 (BMP4), transcript variant 5, mRNA
Homo sapiens bone morphogenetic protein 4 (BMP4), transcript variant 5, mRNA
gi|1122781518|ref|NM_001347913.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002603389	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Likely pathogenic (Jan 6, 2022)	unknown	clinical testing	Citation Link,
SCV003196349	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9973285, 11590124, 34704412, 28492532
SCV004210889	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 22, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002603389

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Likely pathogenic
(Jan 6, 2022)

unknown

clinical testing

Citation Link,

SCV003196349

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004210889

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 22, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	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 (5)

Details of each submission

From Myriad Genetics, Inc., SCV002603389.2

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

Description

NM_000018.3(ACADVL):c.1522C>T(Q508*) is expected to be pathogenic in the context of very-long-chain acyl-CoA dehydrogenase deficiency. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in ACADVL, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003196349.2

#	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 creates a premature translational stop signal (p.Gln508*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 34704412). ClinVar contains an entry for this variant (Variation ID: 1726981). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as 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

From Baylor Genetics, SCV004210889.2

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

Last Updated: Sep 29, 2024

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