NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Uncertain significance (Last evaluated: May 17, 2018)

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:
RCV000652029.3

Allele description [Variation Report for NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)]

NM_000018.4(ACADVL):c.1591C>T (p.Arg531Trp)

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.1591C>T (p.Arg531Trp)
HGVS:
  • NC_000017.11:g.7224379C>T
  • NG_007975.1:g.9546C>T
  • NM_000018.4:c.1591C>T
  • NM_001270448.1:c.1363C>T
  • NP_000009.1:p.Arg531Trp
  • NP_001257377.1:p.Arg455Trp
  • NC_000017.10:g.7127698C>T
  • NM_000018.3:c.1591C>T
Protein change:
R455W
Links:
dbSNP: rs146379816
NCBI 1000 Genomes Browser:
rs146379816
Molecular consequence:
  • NM_000018.3:c.1591C>T - 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
SCV000773889Invitaecriteria provided, single submitter
Uncertain significance
(May 17, 2018)
germlineclinical testing

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

SCV000791958Counsylcriteria provided, single submitter
Uncertain significance
(Jun 5, 2017)
unknownclinical testing

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

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

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

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
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000773889.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with tryptophan at codon 531 of the ACADVL protein (p.Arg531Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs146379816, ExAC 0.08%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 21932095). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as p.Arg491Trp in the literature. ClinVar contains an entry for this variant (Variation ID: 166647). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Counsyl, SCV000791958.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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