Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: ACADVL vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000018.4(ACADVL):c.1878G>A (p.Trp626Ter)

CA397726083

541724 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: ccd31cd4-cbd4-4254-a595-ba9daa135e32
Approved on: 2025-04-22
Published on: 2025-04-25

HGVS expressions

NM_000018.4:c.1878G>A
NM_000018.4(ACADVL):c.1878G>A (p.Trp626Ter)
NC_000017.11:g.7225007G>A
CM000679.2:g.7225007G>A
NC_000017.10:g.7128326G>A
CM000679.1:g.7128326G>A
NC_000017.9:g.7069050G>A
NG_007975.1:g.10174G>A
NG_008391.2:g.44C>T
NG_033038.1:g.14538C>T
ENST00000356839.10:c.1878G>A
ENST00000322910.9:c.*1833G>A
ENST00000350303.9:c.1812G>A
ENST00000356839.9:c.1878G>A
ENST00000542255.6:c.757G>A
ENST00000543245.6:c.1947G>A
ENST00000578033.1:n.303G>A
ENST00000578319.5:n.459G>A
ENST00000578711.1:n.1503G>A
ENST00000578809.5:n.450G>A
ENST00000579425.5:n.994G>A
ENST00000583848.5:c.244G>A
ENST00000583850.5:n.649G>A
ENST00000583858.5:c.809G>A
NM_000018.3:c.1878G>A
NM_001033859.2:c.1812G>A
NM_001270447.1:c.1947G>A
NM_001270448.1:c.1650G>A
NM_001033859.3:c.1812G>A
NM_001270447.2:c.1947G>A
NM_001270448.2:c.1650G>A
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Uncertain Significance

Met criteria codes 2
PVS1_Moderate PM2
Not Met criteria codes 1
PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.1878G>A p.(Trp626Ter) variant in ACADVL is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate; PMIDs 9973285, 11590124). This variant has been reported in the literature in individuals undergoing newborn screening (PMIDs: 32778825, 26385305), however, the phenotype or if a second ACADVL variant was detected in trans in these individuals was not reported. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00002891 in Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as variant of uncertain significance 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: PVS1_Moderate, PM2_supporting (ACADVL VCEP specifications version 1; approved November 9, 2021).
Met criteria codes
PVS1_Moderate
The c.1878G>A p.(Trp626Ter) variant in ACADVL is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate; PMIDs 9973285, 11590124).
PM2
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Not Met criteria codes
PM3
No patients described. Mentioned in 2 papers in sup tables but no patient details or genotypes.
Curation History
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