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_001270448.2:c.1216_1220del

CA1139532272

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6b627388-e99e-4753-83c5-3ed91fbfd961

Approved on: 2023-06-27

Published on: 2023-06-27

HGVS expressions

NM_001270448.2:c.1216_1220del

NC_000017.11:g.7224155_7224159del

CM000679.2:g.7224155_7224159del

NC_000017.10:g.7127474_7127478del

CM000679.1:g.7127474_7127478del

NC_000017.9:g.7068198_7068202del

NG_007975.1:g.9322_9326del

NG_008391.2:g.898_902del

NG_033038.1:g.15392_15396del

ENST00000356839.10:c.1444_1448del

ENST00000322910.9:c.*1399_*1403del

ENST00000350303.9:c.1378_1382del

ENST00000356839.9:c.1444_1448del

ENST00000542255.6:n.302_306del

ENST00000543245.6:c.1513_1517del

ENST00000578711.1:n.651_655del

ENST00000579391.1:n.52_56del

ENST00000579425.5:n.560_564del

ENST00000579546.1:n.271+86_271+90del

ENST00000579894.5:n.231_235del

ENST00000583074.5:n.153+86_153+90del

ENST00000583850.5:n.219_223del

ENST00000583858.5:n.463+86_463+90del

ENST00000585203.6:n.635_639del

NM_000018.3:c.1444_1448del

NM_001033859.2:c.1378_1382del

NM_001270447.1:c.1513_1517del

NM_001270448.1:c.1216_1220del

NM_000018.4:c.1444_1448del

NM_001033859.3:c.1378_1382del

NM_001270447.2:c.1513_1517del

Pathogenic

PVS1 PP4 PM3_Supporting 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.1444_1448del variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 15/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1: PMIDs 9973285, 11590124). This variant was reported in a patient with ACADVL deficiency who carried the pathogenic p.Val283Ala allele(PM3_Supporting, PMID: 25834949). Deficient VLCAD enzyme activity (below 20% of normal) was also measured from this patient's cultured fibroblasts (PP4, PMID: 25834949). This variant is absent from population databases gnomAD v2.1.1 (PM2_supporting). In summary the ACADVL Variant Curation Expert Panel VCEP classified the variant as pathogenic based on PVS1+PM2_Supporting+PM3_supporting+PP4.

PVS1

Frameshift in exon 15/20

PP4

Enzyme activity below 10% of control (figure 1b). Other parameters are reported, but not certain how to apply to our guidelines (figure 1).

PM3_Supporting

Phase unknown, but trans het. with common V283A allele

PM2_Supporting

Absent from gnomAD

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