NM_000018.4(ACADVL):c.1147C>G (p.Leu383Val) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jul 15, 2022
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:: RCV001200752.5

Allele description [Variation Report for NM_000018.4(ACADVL):c.1147C>G (p.Leu383Val)]

NM_000018.4(ACADVL):c.1147C>G (p.Leu383Val)

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.1147C>G (p.Leu383Val)

HGVS:

NC_000017.11:g.7223202C>G
NG_007975.1:g.8369C>G
NG_008391.2:g.1849G>C
NM_000018.4:c.1147C>GMANE SELECT
NM_001033859.3:c.1081C>G
NM_001270447.2:c.1216C>G
NM_001270448.2:c.919C>G
NP_000009.1:p.Leu383Val
NP_001029031.1:p.Leu361Val
NP_001257376.1:p.Leu406Val
NP_001257377.1:p.Leu307Val
NC_000017.10:g.7126521C>G
NC_000017.10:g.7126521C>G
NM_000018.3:c.1147C>G

Protein change:

L307V

Links:

dbSNP: rs756194870

NCBI 1000 Genomes Browser:

rs756194870

Molecular consequence:

NM_000018.4:c.1147C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1081C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1216C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.919C>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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cytochrome b, partial (mitochondrion) [Panaspis annobonensis]
cytochrome b, partial (mitochondrion) [Panaspis annobonensis]
gi|158121061|gb|ABW16982.1|

Protein
RecName: Full=25S rRNA (cytosine(2278)-C(5))-methyltransferase; AltName: Full=rR...
RecName: Full=25S rRNA (cytosine(2278)-C(5))-methyltransferase; AltName: Full=rRNA m(5)C methyltransferase 1
gi|1730712|sp|P53972.1|RCM1_YEAST

Protein
sucrose synthase [Salvia splendens]
sucrose synthase [Salvia splendens]
gi|2060368580|ref|XP_042002877.1|

Protein
miRNA_SPF-ABT-4
miRNA_SPF-ABT-4

GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001365082	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]
SCV002171323	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002791834	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 18, 2021)	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

SCV001365082

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]

SCV002171323

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 15, 2022)

germline

clinical testing

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

SCV002791834

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 18, 2021)

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

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

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

Details of each submission

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001365082.2

#	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.1147C>G (NP_000009.1:p.Leu383Val) [GRCH38: NC_000017.11:g.7223202C>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: BP4

#	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, SCV002171323.2

#	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 leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 383 of the ACADVL protein (p.Leu383Val). This variant is present in population databases (rs756194870, 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: 932803). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 Fulgent Genetics, Fulgent Genetics, SCV002791834.1

#	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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