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.541dup (p.His181fs)

CA397723118

932736 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: c7fb4c7f-e8f1-4b85-8190-55c2f183f3eb

Approved on: 2022-03-08

Published on: 2022-04-28

HGVS expressions

NM_000018.4:c.541dup

NM_000018.4(ACADVL):c.541dup (p.His181fs)

NC_000017.11:g.7221601dup

CM000679.2:g.7221601dup

NC_000017.10:g.7124920dup

CM000679.1:g.7124920dup

NC_000017.9:g.7065644dup

NG_007975.1:g.6768dup

NG_008391.2:g.3452dup

ENST00000356839.10:c.541dup

ENST00000322910.9:c.*496dup

ENST00000350303.9:c.475dup

ENST00000356839.9:c.541dup

ENST00000543245.6:c.610dup

ENST00000577191.5:n.618dup

ENST00000577433.5:n.749dup

ENST00000577857.5:n.357dup

ENST00000579286.5:n.722dup

ENST00000579886.2:c.379dup

ENST00000580365.1:n.272dup

ENST00000581378.5:n.259dup

ENST00000581562.5:n.525-351dup

ENST00000582166.1:n.522dup

ENST00000583312.5:c.541dup

ENST00000583760.1:n.323dup

NM_000018.3:c.541dup

NM_001033859.2:c.475dup

NM_001270447.1:c.610dup

NM_001270448.1:c.313dup

NM_001033859.3:c.475dup

NM_001270447.2:c.610dup

NM_001270448.2:c.313dup

Pathogenic

PVS1 PM2_Supporting PP4_Moderate

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.541dup (p.His181fs)variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one patient with this variant displayed enzyme activity levels measured in lymphocytes of 6% of control values, which is highly specific for VLCAD deficiency (PP4_moderate, PMID 32463482). 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 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, PP4_moderate, PM2_supporting. VCEP specifications version2; 10/15/21.

PVS1

PM2_Supporting

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

PP4_Moderate

At least one patient with this variant displayed enzyme levels measured in lymphocytes of 6% of control values, which is highly specific for VLCAD deficiency (PP4_moderate, PMID 32463482).

PM3

This variant is reported in unconfirmed trans with another variant (c.1072A>G (p.Lys358Glu)) but this second variant is currently a VUS according to VCEP classification criteria and therefore no points are applied to PM3 for this evaluation.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.