Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000018.4(ACADVL):c.364A>G (p.Asn122Asp)

CA16603209

376917 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f3e3957f-6574-4967-8c18-68fb22f8685e

HGVS expressions

NM_000018.4:c.364A>G

NM_000018.4(ACADVL):c.364A>G (p.Asn122Asp)

NC_000017.11:g.7220945A>G

CM000679.2:g.7220945A>G

NC_000017.10:g.7124264A>G

CM000679.1:g.7124264A>G

NC_000017.9:g.7064988A>G

NG_007975.1:g.6112A>G

NG_008391.2:g.4106T>C

ENST00000356839.10:c.364A>G

ENST00000322910.9:c.*319A>G

ENST00000350303.9:c.298A>G

ENST00000356839.9:c.364A>G

ENST00000543245.6:c.433A>G

ENST00000577191.5:n.441A>G

ENST00000577433.5:n.572A>G

ENST00000577857.5:n.293+115A>G

ENST00000579286.5:n.545A>G

ENST00000579886.2:c.202A>G

ENST00000580365.1:n.95A>G

ENST00000581378.5:n.63A>G

ENST00000581562.5:n.411A>G

ENST00000582056.5:n.547A>G

ENST00000582166.1:n.345A>G

ENST00000583312.5:c.364A>G

ENST00000584103.5:c.397A>G

NM_000018.3:c.364A>G

NM_001033859.2:c.298A>G

NM_001270447.1:c.433A>G

NM_001270448.1:c.136A>G

NM_001033859.3:c.298A>G

NM_001270447.2:c.433A>G

NM_001270448.2:c.136A>G

Likely Pathogenic

PM2_Supporting PP3 PP4 PS3

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.364A>G (p.Asn122Asp) variant in ACADVL is a missense in exon 6. This variant has been reported as a homozygote in the literature associated with very-long chain acyl-CoA dehydrogenase deficiency (PP4; PMID: 34480364). Fatty acid oxidation (FAO) flux assay performed on patient fibroblast homozygous for this variant demonstrated severe reduction of enzyme activity (PS3, PMID: 20060901). In additon, protein production was deficient for this genotype shown by western blot (PMID: 20060901). This variant is absent from population databases gnomAD v2.1.1 (PM2_supporting). The computational predictor REVEL gives a score of 0.86, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: (PP4,PP3, PS3, PM2_Supporting).

PM2_Supporting

Absent from gnomAD

PP3

0.856 REVEL

PP4

Detected as a homozygote in patient with VLCAD deficiency.

PS3

Severely reduces enzyme activity in a FAO flux Severely reduced protein level by western Disrupts hydrogen bonding network of nearby residues.

Approved on: 2022-05-06

Published on: 2022-05-10

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