NM_000018.4(ACADVL):c.505A>G (p.Met169Val) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 10, 2023
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:: RCV001200825.3

Allele description [Variation Report for NM_000018.4(ACADVL):c.505A>G (p.Met169Val)]

NM_000018.4(ACADVL):c.505A>G (p.Met169Val)

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.505A>G (p.Met169Val)

HGVS:

NC_000017.11:g.7221565A>G
NG_007975.1:g.6732A>G
NG_008391.2:g.3486T>C
NM_000018.4:c.505A>GMANE SELECT
NM_001033859.3:c.439A>G
NM_001270447.2:c.574A>G
NM_001270448.2:c.277A>G
NP_000009.1:p.Met169Val
NP_001029031.1:p.Met147Val
NP_001257376.1:p.Met192Val
NP_001257377.1:p.Met93Val
NC_000017.10:g.7124884A>G
NC_000017.10:g.7124884A>G
NM_000018.3:c.505A>G

Protein change:

M147V

Links:

dbSNP: rs2071227343

NCBI 1000 Genomes Browser:

rs2071227343

Molecular consequence:

NM_000018.4:c.505A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.439A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.574A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.277A>G - 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

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putative exo-rhamnogalacturonase C [Aspergillus niger]
putative exo-rhamnogalacturonase C [Aspergillus niger]
gi|89113914|gb|ABD61568.1|

Protein
Zea m 13 allergen [Zea mays]
Zea m 13 allergen [Zea mays]
gi|89892725|gb|ABD79096.1|

Protein
At3g59850 [Arabidopsis thaliana]
At3g59850 [Arabidopsis thaliana]
gi|53749142|gb|AAU90056.1|

Protein
cytochrome c oxidase subunit I, partial (mitochondrion) [Scomberomorus koreanus]
cytochrome c oxidase subunit I, partial (mitochondrion) [Scomberomorus koreanus]
gi|2184130289|gb|UJT44327.1|

Protein
FGSG_10708 [Fusarium graminearum PH-1]
FGSG_10708 [Fusarium graminearum PH-1]
Gene ID:23557596

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001365026	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]
SCV004261829	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 10, 2023)	germline	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

SCV001365026

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]

SCV004261829

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 10, 2023)

germline

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365026.2

#	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.505A>G (NP_000009.1:p.Met169Val) [GRCH38: NC_000017.11:g.7221565A>G] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PM1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004261829.1

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 169 of the ACADVL protein (p.Met169Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 932865). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACADVL protein function. 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

Last Updated: Sep 29, 2024

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