NM_000018.4(ACADVL):c.1154G>A (p.Arg385Gln) AND Very long chain acyl-CoA dehydrogenase deficiency

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

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Dec 1, 2023
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:: RCV001043789.7

Allele description

NM_000018.4(ACADVL):c.1154G>A (p.Arg385Gln)

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.1154G>A (p.Arg385Gln)

HGVS:

NC_000017.11:g.7223209G>A
NG_007975.1:g.8376G>A
NG_008391.2:g.1842C>T
NM_000018.4:c.1154G>AMANE SELECT
NM_001033859.3:c.1088G>A
NM_001270447.2:c.1223G>A
NM_001270448.2:c.926G>A
NP_000009.1:p.Arg385Gln
NP_001029031.1:p.Arg363Gln
NP_001257376.1:p.Arg408Gln
NP_001257377.1:p.Arg309Gln
NC_000017.10:g.7126528G>A
NC_000017.10:g.7126528G>A
NM_000018.3:c.1154G>A

Protein change:

R309Q

Links:

dbSNP: rs772014118

NCBI 1000 Genomes Browser:

rs772014118

Molecular consequence:

NM_000018.4:c.1154G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1088G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.926G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001207553	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 1, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 15210884, 23798014, 25655073, 28755359, 32655480, 28492532
SCV001365083	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 1, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002088782	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jul 2, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001207553

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 1, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001365083

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 1, 2019)

germline

clinical testing

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

SCV002088782

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jul 2, 2020)

germline

clinical testing

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

A new diagnostic test for VLCAD deficiency using immunohistochemistry.

Ohashi Y, Hasegawa Y, Murayama K, Ogawa M, Hasegawa T, Kawai M, Sakata N, Yoshida K, Yarita H, Imai K, Kumagai I, Murakami K, Hasegawa H, Noguchi S, Nonaka I, Yamaguchi S, Nishino I.

Neurology. 2004 Jun 22;62(12):2209-13.

PubMed [citation]

PMID:: 15210884

Neuropsychological outcomes in fatty acid oxidation disorders: 85 cases detected by newborn screening.

Waisbren SE, Landau Y, Wilson J, Vockley J.

Dev Disabil Res Rev. 2013;17(3):260-8. doi: 10.1002/ddrr.1119.

PubMed [citation]

PMID:: 23798014
PMCID:: PMC4137760

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001207553.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 385 of the ACADVL protein (p.Arg385Gln). This variant is present in population databases (rs772014118, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. ClinVar contains an entry for this variant (Variation ID: 841542). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACADVL protein function with a positive predictive value of 95%. This variant disrupts the p.Arg385 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15210884, 23798014, 25655073, 28755359, 32655480). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been 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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365083.2

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

Description

The NM_000018.3:c.1154G>A (NP_000009.1:p.Arg385Gln) [GRCH38: NC_000017.11:g.7223209G>A] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant dose not meet any evidence codes reported in the ACMG guidelines.

#	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 Natera, Inc., SCV002088782.1

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

#	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: May 26, 2024

ClinVar

Relating variation to medicine