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

CA8338094

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9f4817fc-33b3-41b4-96fa-ed2ff0e5fa13

Approved on: 2023-11-28

Published on: 2023-11-28

HGVS expressions

NM_001270448.2:c.1183T>C

NC_000017.11:g.7224046T>C

CM000679.2:g.7224046T>C

NC_000017.10:g.7127365T>C

CM000679.1:g.7127365T>C

NC_000017.9:g.7068089T>C

NG_007975.1:g.9213T>C

NG_008391.2:g.1005A>G

NG_033038.1:g.15499A>G

ENST00000356839.10:c.1411T>C

ENST00000322910.9:c.*1366T>C

ENST00000350303.9:c.1345T>C

ENST00000356839.9:c.1411T>C

ENST00000542255.6:c.269T>C

ENST00000543245.6:c.1480T>C

ENST00000578711.1:n.542T>C

ENST00000579425.5:n.527T>C

ENST00000579546.1:c.248T>C

ENST00000579894.5:n.122T>C

ENST00000583074.5:n.130T>C

ENST00000583850.5:n.186T>C

ENST00000583858.5:c.440T>C

ENST00000585203.6:n.602T>C

NM_000018.3:c.1411T>C

NM_001033859.2:c.1345T>C

NM_001270447.1:c.1480T>C

NM_001270448.1:c.1183T>C

NM_000018.4:c.1411T>C

NM_001033859.3:c.1345T>C

NM_001270447.2:c.1480T>C

Uncertain Significance

PP3 PM3_Supporting PP4_Moderate PM2_Supporting

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

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).

PP3

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).

PM3_Supporting

Detected in the homozygous state

PP4_Moderate

Reduced very long chain acyl CoA dehydrogenase (VLCAD) enzyme activity

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

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