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]

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Variant: NM_000018.4(ACADVL):c.1194C>A (p.Tyr398Ter)

CA397724566

810875 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bdfee8c1-453c-447d-afac-9ae7b0c1263b

HGVS expressions

NM_000018.4:c.1194C>A

NM_000018.4(ACADVL):c.1194C>A (p.Tyr398Ter)

NC_000017.11:g.7223655C>A

CM000679.2:g.7223655C>A

NC_000017.10:g.7126974C>A

CM000679.1:g.7126974C>A

NC_000017.9:g.7067698C>A

NG_007975.1:g.8822C>A

NG_008391.2:g.1396G>T

NG_033038.1:g.15890G>T

ENST00000356839.10:c.1194C>A

ENST00000322910.9:c.*1149C>A

ENST00000350303.9:c.1128C>A

ENST00000356839.9:c.1194C>A

ENST00000542255.6:n.52C>A

ENST00000543245.6:c.1263C>A

ENST00000578579.2:n.365C>A

ENST00000578711.1:n.151C>A

ENST00000578824.5:n.610C>A

ENST00000579425.5:n.218C>A

ENST00000579546.1:n.31C>A

ENST00000583858.5:n.223C>A

ENST00000585203.6:n.402C>A

NM_000018.3:c.1194C>A

NM_001033859.2:c.1128C>A

NM_001270447.1:c.1263C>A

NM_001270448.1:c.966C>A

NM_001033859.3:c.1128C>A

NM_001270447.2:c.1263C>A

NM_001270448.2:c.966C>A

Pathogenic

PP4_Moderate PM2_Supporting PVS1

PM3

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1194C>A (p.Tyr398Ter) variant in ACADVL is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 12/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). This variant has been described in an individual with increased C14:1 acylcarnitine and fibroblasts derived from this individual showed a significantly reduced VLCAD enzyme activity, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4_moderate, PMID: 10529389). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PP4_moderate, PM2_Supporting (ACADVL VCEP specifications version 1; approved November 8, 2021).

PP4_Moderate

This variant has been described in an individual with increased C14:1 acylcarnitine and fibroblasts derived from this individual showed a significantly reduced VLCAD enzyme activity, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4_moderate, PMID: 10529389).

PM2_Supporting

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

PVS1

PM3

Detected confirmed in trans (by cloning) to c.953C>T (p.Pro318Leu), likely path/path in ClinVar (Variation ID: 439361), but not yet curated by VCEP (PMID: 10529389).

Approved on: 2022-12-14

Published on: 2022-12-14

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