NM_000018.3(ACADVL):c.637G>C (p.Ala213Pro) AND Very long chain acyl-CoA dehydrogenase deficiency

Clinical significance:Uncertain significance (Last evaluated: May 18, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000702574.1

Allele description [Variation Report for NM_000018.3(ACADVL):c.637G>C (p.Ala213Pro)]

NM_000018.3(ACADVL):c.637G>C (p.Ala213Pro)

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.637G>C (p.Ala213Pro)
HGVS:
  • NC_000017.11:g.7221966G>C
  • NG_007975.1:g.7133G>C
  • NM_000018.3:c.637G>C
  • NP_000009.1:p.Ala213Pro
  • NC_000017.10:g.7125285G>C
  • P49748:p.Ala213Pro
Protein change:
A213P
Links:
UniProtKB: P49748#VAR_010101; dbSNP: rs140629318
NCBI 1000 Genomes Browser:
rs140629318
Molecular consequence:
  • NM_000018.3:c.637G>C - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000831433Invitaecriteria provided, single submitter
Uncertain significance
(May 18, 2018)
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, SCV000831433.1

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

Description

This sequence change replaces alanine with proline at codon 213 of the ACADVL protein (p.Ala213Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant is present in population databases (rs140629318, ExAC 0.01%). This variant has been observed to be homozygous in an individual affected with very long chain acyl-CoA dehydrogenase deficiency (PMID: 10077518). ClinVar contains an entry for this variant (Variation ID: 166643). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Ala213Pro and p.Ala231Thr) in affected individuals suggests that this may be a clinically significant residue (PMID: 12213615). 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

Last Updated: Mar 30, 2019

Support Center