NM_000018.4(ACADVL):c.433C>T (p.Gln145Ter) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Likely pathogenic (4 submissions)
Last evaluated:: Mar 8, 2022
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000169585.14

Allele description [Variation Report for NM_000018.4(ACADVL):c.433C>T (p.Gln145Ter)]

NM_000018.4(ACADVL):c.433C>T (p.Gln145Ter)

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.433C>T (p.Gln145Ter)

Other names:

NM_000018.4(ACADVL):c.433C>T; p.Gln145Ter

HGVS:

NC_000017.11:g.7221014C>T
NG_007975.1:g.6181C>T
NG_008391.2:g.4037G>A
NM_000018.4:c.433C>TMANE SELECT
NM_001033859.3:c.367C>T
NM_001270447.2:c.502C>T
NM_001270448.2:c.205C>T
NP_000009.1:p.Gln145Ter
NP_001029031.1:p.Gln123Ter
NP_001257376.1:p.Gln168Ter
NP_001257377.1:p.Gln69Ter
NC_000017.10:g.7124333C>T
NM_000018.3:c.433C>T

Protein change:

Q123*

Links:

dbSNP: rs786204738

NCBI 1000 Genomes Browser:

rs786204738

Molecular consequence:

NM_000018.4:c.433C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001033859.3:c.367C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001270447.2:c.502C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001270448.2:c.205C>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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000221092	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jan 28, 2015)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 10384387, 9973285 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV001410923	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 19, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10384387, 9973285, 11590124, 28492532
SCV002576783	ClinGen ACADVL Variant Curation Expert Panel, ClinGen	reviewed by expert panel (clingen acadvl acmg specifications v1)	Likely pathogenic (Mar 8, 2022)	germline	curation	Citation Link,
SCV004210856	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 27, 2023)	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, curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, literature only

Citations

PubMed

DNA-based prenatal diagnosis for very-long-chain acyl-CoA dehydrogenase deficiency.

Andresen BS, Olpin S, Kvittingen EA, Augoustides-Savvopoulou P, Lindhout D, Halley DJ, Vianey-Saban C, Wanders RJ, Ijlst L, Schroeder LD, Bolund L, Gregersen N.

J Inherit Metab Dis. 1999 May;22(3):281-5. No abstract available.

PubMed [citation]

PMID:: 10384387

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

See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000221092.2

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

#	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, SCV001410923.5

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

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 189159). This variant is also known as Q105X. This premature translational stop signal has been observed in individual(s) with ACADVL-related conditions (PMID: 9973285, 10384387). This sequence change creates a premature translational stop signal (p.Gln145*) 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

From ClinGen ACADVL Variant Curation Expert Panel, ClinGen, SCV002576783.2

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

Description

The c.433C>T (p.Gln145Ter) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 6/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). This variant is absent from gnomAD v2.11 (PM2_Supporting). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1+PM2_supporting (VCEP specifications v2.0, approved on 09/16/2021).

#	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, SCV004210856.2

#	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

ClinVar

Relating variation to medicine