NM_000018.3(ACADVL):c.339C>A (p.Phe113Leu) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Uncertain significance (Last evaluated: Dec 21, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000541584.1

Allele description [Variation Report for NM_000018.3(ACADVL):c.339C>A (p.Phe113Leu)]

NM_000018.3(ACADVL):c.339C>A (p.Phe113Leu)

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_000018.3(ACADVL):c.339C>A (p.Phe113Leu)
HGVS:
  • NC_000017.11:g.7220827C>A
  • NG_007975.1:g.5994C>A
  • NM_000018.3:c.339C>A
  • NP_000009.1:p.Phe113Leu
  • NC_000017.10:g.7124146C>A
Protein change:
F113L
Links:
dbSNP: rs750653177
NCBI 1000 Genomes Browser:
rs750653177
Molecular consequence:
  • NM_000018.3:c.339C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000654951Invitaecriteria provided, single submitter
Uncertain significance
(Dec 21, 2016)
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

Citations

PubMed

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.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000654951.1

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

Description

This sequence change replaces phenylalanine with leucine at codon 113 of the ACADVL protein (p.Phe113Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). In an individual suspected with VLCAD deficiency identified through newborn screening, this variant was observed as compound heterozygous with a known pathogenic variant p.Val243Ala. In this previously reported compound heterozygous individual, the residual enzyme activity is 22% in the lymphocytes (PMID: 21932095); however, the independent impact of this variant has not been assessed. This variant is also known as F73L in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare missense change with uncertain impact on protein function and RNA splicing. It has been classified as a Variant of Uncertain Significance.

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

Last Updated: Mar 30, 2019

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