NM_000018.4(ACADVL):c.956C>A (p.Ser319Ter) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Apr 16, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000673848.2

Allele description [Variation Report for NM_000018.4(ACADVL):c.956C>A (p.Ser319Ter)]

NM_000018.4(ACADVL):c.956C>A (p.Ser319Ter)

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.956C>A (p.Ser319Ter)
HGVS:
  • NC_000017.11:g.7222744C>A
  • NG_007975.1:g.7911C>A
  • NG_008391.2:g.2307G>T
  • NM_000018.4:c.956C>AMANE SELECT
  • NM_001033859.2:c.890C>A
  • NM_001270447.1:c.1025C>A
  • NM_001270448.1:c.728C>A
  • NP_000009.1:p.Ser319Ter
  • NP_001029031.1:p.Ser297Ter
  • NP_001257376.1:p.Ser342Ter
  • NP_001257377.1:p.Ser243Ter
  • NC_000017.10:g.7126063C>A
  • NM_000018.3:c.956C>A
Protein change:
S243*
Links:
dbSNP: rs149467828
NCBI 1000 Genomes Browser:
rs149467828
Molecular consequence:
  • NM_000018.4:c.956C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001033859.2:c.890C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001270447.1:c.1025C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001270448.1:c.728C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (VLCAD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000799096Counsylcriteria provided, single submitter
Likely pathogenic
(Apr 12, 2018)
unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV001473604ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(Apr 16, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Citations

PubMed

Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database.

Pena LD, van Calcar SC, Hansen J, Edick MJ, Walsh Vockley C, Leslie N, Cameron C, Mohsen AW, Berry SA, Arnold GL, Vockley J; IBEMC..

Mol Genet Metab. 2016 Aug;118(4):272-81. doi: 10.1016/j.ymgme.2016.05.007. Epub 2016 May 13.

PubMed [citation]
PMID:
27209629
PMCID:
PMC4970910

Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.

Tabor HK, Auer PL, Jamal SM, Chong JX, Yu JH, Gordon AS, Graubert TA, O'Donnell CJ, Rich SS, Nickerson DA; NHLBI Exome Sequencing Project., Bamshad MJ.

Am J Hum Genet. 2014 Aug 7;95(2):183-93. doi: 10.1016/j.ajhg.2014.07.006. Epub 2014 Jul 31.

PubMed [citation]
PMID:
25087612
PMCID:
PMC4129409

Details of each submission

From Counsyl, SCV000799096.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories, SCV001473604.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ACADVL c.956C>A p.Ser319Ter variant (rs149467828) is reported in the literature in at least one individual affected with very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency (Pena 2016). This variant is reported in ClinVar (Variation ID: 557676), and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, several downstream truncating variants have been described in individuals with VLCAD deficiency and are considered pathogenic (Pena 2016). Based on available information, this variant is considered to be pathogenic. References: Pena LD et al. Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database. Mol Genet Metab. 2016 Aug;118(4):272-81.

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

Last Updated: Apr 12, 2021

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