NM_000018.4(ACADVL):c.308_309del (p.Lys103fs) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 1, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000410821.4

Allele description [Variation Report for NM_000018.4(ACADVL):c.308_309del (p.Lys103fs)]

NM_000018.4(ACADVL):c.308_309del (p.Lys103fs)

Gene:
ACADVL:acyl-CoA dehydrogenase very long chain [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000018.4(ACADVL):c.308_309del (p.Lys103fs)
HGVS:
  • NC_000017.11:g.7220796_7220797del
  • NG_007975.1:g.5963_5964del
  • NG_008391.2:g.4255_4256del
  • NM_000018.4:c.308_309delMANE SELECT
  • NM_001033859.2:c.242_243del
  • NM_001270447.1:c.377_378del
  • NM_001270448.1:c.80_81del
  • NP_000009.1:p.Lys103fs
  • NP_001029031.1:p.Lys81fs
  • NP_001257376.1:p.Lys126fs
  • NP_001257377.1:p.Lys27fs
  • NC_000017.10:g.7124114_7124115del
  • NC_000017.10:g.7124115_7124116del
  • NM_000018.2:c.308_309delAA
  • NM_000018.3:c.308_309del
  • NM_000018.3:c.308_309delAA
Protein change:
K103fs
Links:
dbSNP: rs1057516979
NCBI 1000 Genomes Browser:
rs1057516979
Molecular consequence:
  • NM_000018.4:c.308_309del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001033859.2:c.242_243del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001270447.1:c.377_378del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001270448.1:c.80_81del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000486537Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 21, 2016)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001236379Invitaecriteria provided, single submitter
Pathogenic
(Jan 24, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001364956Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicinecriteria provided, single submitter
Pathogenic
(Nov 1, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

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

Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States.

Miller MJ, Burrage LC, Gibson JB, Strenk ME, Lose EJ, Bick DP, Elsea SH, Sutton VR, Sun Q, Graham BH, Craigen WJ, Zhang VW, Wong LJ.

Mol Genet Metab. 2015 Nov;116(3):139-45. doi: 10.1016/j.ymgme.2015.08.011. Epub 2015 Sep 2.

PubMed [citation]
PMID:
26385305
PMCID:
PMC4790081

Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

Andresen BS, Olpin S, Poorthuis BJ, Scholte HR, Vianey-Saban C, Wanders R, Ijlst L, Morris A, Pourfarzam M, Bartlett K, Baumgartner ER, deKlerk JB, Schroeder LD, Corydon TJ, Lund H, Winter V, Bross P, Bolund L, Gregersen N.

Am J Hum Genet. 1999 Feb;64(2):479-94.

PubMed [citation]
PMID:
9973285
PMCID:
PMC1377757
See all PubMed Citations (5)

Details of each submission

From Counsyl, SCV000486537.1

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

From Invitae, SCV001236379.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Lys103Argfs*20) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with abnormal newborn screening results suggestive of VLCADD (PMID: 26385305). ClinVar contains an entry for this variant (Variation ID: 371068). Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). For these reasons, this variant has been classified as Pathogenic.

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

From Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV001364956.2

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

Description

The NM_000018.3:c.308_309delAA (NP_000009.1:p.Lys103ArgfsTer20) [GRCH38: NC_000017.11:g.7220796_7220797del] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3

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

Last Updated: Sep 6, 2021

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