NM_000018.3(ACADVL):c.1273G>A (p.Ala425Thr) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Uncertain significance (Last evaluated: Apr 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:
RCV000652034.3

Allele description [Variation Report for NM_000018.3(ACADVL):c.1273G>A (p.Ala425Thr)]

NM_000018.3(ACADVL):c.1273G>A (p.Ala425Thr)

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.1273G>A (p.Ala425Thr)
HGVS:
  • NC_000017.11:g.7223816G>A
  • NG_007975.1:g.8983G>A
  • NM_000018.2:c.1273G>A
  • NM_000018.3:c.1273G>A
  • NP_000009.1:p.Ala425Thr
  • NC_000017.10:g.7127135G>A
Protein change:
A425T
Links:
dbSNP: rs138834083
NCBI 1000 Genomes Browser:
rs138834083
Molecular consequence:
  • NM_000018.3:c.1273G>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
SCV000773895Invitaecriteria provided, single submitter
Uncertain significance
(Apr 17, 2018)
germlineclinical testing

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

SCV000800548Counsylcriteria provided, single submitter
Uncertain significance
(Jun 19, 2017)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

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

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
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000773895.2

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

Description

This sequence change replaces alanine with threonine at codon 425 of the ACADVL protein (p.Ala425Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs138834083, ExAC 0.04%). This variant has been reported in combination with another ACADVL variant in individuals affected with very long chain acyl-CoA dehydrogenase deficiency (PMID: 27209629, 23700290, Invitae). It has also been reported in combination with another ACADVL variant in several individuals who had a newborn screen suggestive of this condition, and in individuals for whom a second allele was not specified (PMID: 26385305, 20694756). ClinVar contains an entry for this variant (Variation ID: 92273). 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: "Tolerated"; PolyPhen-2: "Probably 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, SCV000800548.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2019

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