NM_000018.4(ACADVL):c.526A>C (p.Ile176Leu) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001326138.6

Allele description [Variation Report for NM_000018.4(ACADVL):c.526A>C (p.Ile176Leu)]

NM_000018.4(ACADVL):c.526A>C (p.Ile176Leu)

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.526A>C (p.Ile176Leu)

HGVS:

NC_000017.11:g.7221586A>C
NG_007975.1:g.6753A>C
NG_008391.2:g.3465T>G
NM_000018.4:c.526A>CMANE SELECT
NM_001033859.3:c.460A>C
NM_001270447.2:c.595A>C
NM_001270448.2:c.298A>C
NP_000009.1:p.Ile176Leu
NP_001029031.1:p.Ile154Leu
NP_001257376.1:p.Ile199Leu
NP_001257377.1:p.Ile100Leu
NC_000017.10:g.7124905A>C

Protein change:

I100L

Links:

dbSNP: rs1300720825

NCBI 1000 Genomes Browser:

rs1300720825

Molecular consequence:

NM_000018.4:c.526A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.460A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.595A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.298A>C - 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

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Thomomys bottae isolate:mThoBot2
Thomomys bottae isolate:mThoBot2
Thomomys bottae (Botta's pocket gopher), mThoBot2, haplotype 1

BioProject
rab5ab RAB5A, member RAS oncogene family, b [Danio rerio]
rab5ab RAB5A, member RAS oncogene family, b [Danio rerio]
Gene ID:393945

Gene
kcmf1 potassium channel modulatory factor 1 [Danio rerio]
kcmf1 potassium channel modulatory factor 1 [Danio rerio]
Gene ID:393927

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001517152	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 31, 2021)	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

SCV001517152

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 31, 2021)

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001517152.3

#	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 isoleucine with leucine at codon 176 of the ACADVL protein (p.Ile176Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with a positive newborn screening result for ACADVL-related disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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