NM_000018.4(ACADVL):c.1315G>T (p.Gly439Cys) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 9, 2019
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:: RCV001233556.8

Allele description [Variation Report for NM_000018.4(ACADVL):c.1315G>T (p.Gly439Cys)]

NM_000018.4(ACADVL):c.1315G>T (p.Gly439Cys)

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.1315G>T (p.Gly439Cys)

HGVS:

NC_000017.11:g.7223858G>T
NG_007975.1:g.9025G>T
NG_008391.2:g.1193C>A
NG_033038.1:g.15687C>A
NM_000018.4:c.1315G>TMANE SELECT
NM_001033859.3:c.1249G>T
NM_001270447.2:c.1384G>T
NM_001270448.2:c.1087G>T
NP_000009.1:p.Gly439Cys
NP_001029031.1:p.Gly417Cys
NP_001257376.1:p.Gly462Cys
NP_001257377.1:p.Gly363Cys
NC_000017.10:g.7127177G>T
NM_000018.3:c.1315G>T

Protein change:

G363C

Links:

dbSNP: rs2071346311

NCBI 1000 Genomes Browser:

rs2071346311

Molecular consequence:

NM_000018.4:c.1315G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001033859.3:c.1249G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270447.2:c.1384G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001270448.2:c.1087G>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001406157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 9, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 2006090, 23480858, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001406157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 9, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

[Programmable and portable infusion pump for advanced cytostatic multidrug treatment].

Småland R, Anker C, Grønlie I, Brøvik K, Lote K, Laerum OD.

Nord Med. 1991;106(2):40-2, 47. Norwegian.

PubMed [citation]

PMID:: 2006090

Molecular and cellular pathology of very-long-chain acyl-CoA dehydrogenase deficiency.

Schiff M, Mohsen AW, Karunanidhi A, McCracken E, Yeasted R, Vockley J.

Mol Genet Metab. 2013 May;109(1):21-7. doi: 10.1016/j.ymgme.2013.02.002. Epub 2013 Feb 13.

PubMed [citation]

PMID:: 23480858
PMCID:: PMC3628282

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001406157.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has been observed in individual(s) with very long-chain acyl-CoA dehydrogenase deficiency (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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. This variant disrupts the p.Gly439 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2006090, 23480858). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: "Probably Damaging"; Align-GVGD: "Class C15"). This sequence change replaces glycine with cysteine at codon 439 of the ACADVL protein (p.Gly439Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency).

#	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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