NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2023
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:: RCV001339031.8

Allele description [Variation Report for NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs)]

NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs)

Gene:

ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs)

HGVS:

NC_000017.11:g.7225038_7225041dup
NG_007975.1:g.10205_10208dup
NG_008391.2:g.10_13dup
NG_033038.1:g.14504_14507dup
NM_000018.4:c.1909_1912dupMANE SELECT
NM_001033859.3:c.1843_1846dup
NM_001270447.2:c.1978_1981dup
NM_001270448.2:c.1681_1684dup
NP_000009.1:p.Ser638fs
NP_001029031.1:p.Ser616fs
NP_001257376.1:p.Ser661fs
NP_001257377.1:p.Ser562fs
NC_000017.10:g.7128356_7128357insATCT
NC_000017.10:g.7128357_7128360dup

Protein change:

S562fs

Links:

dbSNP: rs2071413180

NCBI 1000 Genomes Browser:

rs2071413180

Molecular consequence:

NM_000018.4:c.1909_1912dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001033859.3:c.1843_1846dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270447.2:c.1978_1981dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270448.2:c.1681_1684dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001532746	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31031081, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001532746

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (2)
[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

Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency.

Rovelli V, Manzoni F, Viau K, Pasquali M, Longo N.

Mol Genet Metab. 2019 May;127(1):64-73. doi: 10.1016/j.ymgme.2019.04.001. Epub 2019 Apr 16.

PubMed [citation]

PMID:: 31031081

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, SCV001532746.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a frameshift in the ACADVL gene (p.Ser638Tyrfs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acid(s) of the ACADVL protein and extend the protein by 34 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). 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: 1036078). This variant disrupts a region of the ACADVL protein in which other variant(s) (p.Val642Met) have been determined to be pathogenic (PMID: 31031081). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as 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

Last Updated: Sep 29, 2024

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