U.S. flag

An official website of the United States government

NM_000018.4(ACADVL):c.1411T>C (p.Phe471Leu) AND Very long chain acyl-CoA dehydrogenase deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 28, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003455819.1

Allele description [Variation Report for NM_000018.4(ACADVL):c.1411T>C (p.Phe471Leu)]

NM_000018.4(ACADVL):c.1411T>C (p.Phe471Leu)

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.1411T>C (p.Phe471Leu)
Other names:
NM_001270448.2:c.1183T>C
HGVS:
  • NC_000017.11:g.7224046T>C
  • NG_007975.1:g.9213T>C
  • NG_008391.2:g.1005A>G
  • NG_008391.3:g.1004A>G
  • NG_033038.1:g.15499A>G
  • NM_000018.4:c.1411T>CMANE SELECT
  • NM_001033859.3:c.1345T>C
  • NM_001270447.2:c.1480T>C
  • NM_001270448.2:c.1183T>C
  • NP_000009.1:p.Phe471Leu
  • NP_001029031.1:p.Phe449Leu
  • NP_001257376.1:p.Phe494Leu
  • NP_001257377.1:p.Phe395Leu
  • NC_000017.10:g.7127365T>C
Protein change:
F395L
Molecular consequence:
  • NM_000018.4:c.1411T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001033859.3:c.1345T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270447.2:c.1480T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001270448.2:c.1183T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Very long chain acyl-CoA dehydrogenase deficiency (ACADVLD)
Synonyms:
VLCAD deficiency
Identifiers:
MONDO: MONDO:0008723; MedGen: C3887523; Orphanet: 26793; OMIM: 201475

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004176820ClinGen ACADVL Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(clingen acadvl acmg specifications v1)		Uncertain significance
(Nov 28, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen ACADVL Variant Curation Expert Panel, ClinGen, SCV004176820.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1411T>C (NM_000018.4) variant in ACADVL is a missense variant predicted to cause substitution of phenylalanine by leucine at amino acid 471 (p.Phe471Leu). At least one patient with this variant in the homozygous state displayed reduced very long chain acyl CoA dehydrogenase (VLCAD) enzyme activity, which is highly specific for VLCAD deficiency (PM3_Supporting, PP4_moderate; PMID: 24305961, 25834949). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.838, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). Due to limited evidence, this variant is classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting, PM3_Supporting, PP3, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021).

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

Last Updated: Dec 30, 2023