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NM_000018.4(ACADVL):c.366T>G (p.Asn122Lys) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 29, 2022
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:
RCV003600685.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.366T>G (p.Asn122Lys)]

NM_000018.4(ACADVL):c.366T>G (p.Asn122Lys)

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.366T>G (p.Asn122Lys)
HGVS:
  • NC_000017.11:g.7220947T>G
  • NG_007975.1:g.6114T>G
  • NG_008391.2:g.4104A>C
  • NG_008391.3:g.4103A>C
  • NM_000018.4:c.366T>GMANE SELECT
  • NM_001033859.3:c.300T>G
  • NM_001270447.2:c.435T>G
  • NM_001270448.2:c.138T>G
  • NP_000009.1:p.Asn122Lys
  • NP_001029031.1:p.Asn100Lys
  • NP_001257376.1:p.Asn145Lys
  • NP_001257377.1:p.Asn46Lys
  • NC_000017.10:g.7124266T>G
Protein change:
N100K
Molecular consequence:
  • NM_000018.4:c.366T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.3:c.300T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.2:c.435T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.2:c.138T>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004385425Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 29, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

Gobin-Limballe S, McAndrew RP, Djouadi F, Kim JJ, Bastin J.

Biochim Biophys Acta. 2010 May;1802(5):478-84. doi: 10.1016/j.bbadis.2010.01.001. Epub 2010 Jan 12.

PubMed [citation]
PMID:
20060901
PMCID:
PMC3401415

Development of a Tandem Mass Spectrometry Method for Rapid Measurement of Medium- and Very-Long-Chain Acyl-CoA Dehydrogenase Activity in Fibroblasts.

Bouvier D, Vianey-Saban C, Ruet S, Acquaviva C.

JIMD Rep. 2017;35:71-78. doi: 10.1007/8904_2016_22. Epub 2016 Dec 10.

PubMed [citation]
PMID:
27943070
PMCID:
PMC5585096
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004385425.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 122 of the ACADVL protein (p.Asn122Lys). 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.Asn122 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20060901, 27943070). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with ACADVL-related conditions. This variant is not present in population databases (gnomAD no frequency).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024