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.1317dup (p.Met440fs)

CA913190952

595610 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 16c6eee9-8ad8-4bf5-ad5c-ab5f96fe5ad0

HGVS expressions

NM_000018.4:c.1317dup

NM_000018.4(ACADVL):c.1317dup (p.Met440fs)

NC_000017.11:g.7223860dup

CM000679.2:g.7223860dup

NC_000017.10:g.7127179dup

CM000679.1:g.7127179dup

NC_000017.9:g.7067903dup

NG_007975.1:g.9027dup

NG_008391.2:g.1191dup

NG_033038.1:g.15685dup

ENST00000356839.10:c.1317dup

ENST00000322910.9:c.*1272dup

ENST00000350303.9:c.1251dup

ENST00000356839.9:c.1317dup

ENST00000542255.6:n.175dup

ENST00000543245.6:c.1386dup

ENST00000578711.1:n.356dup

ENST00000579425.5:n.341dup

ENST00000579546.1:n.154dup

ENST00000583074.5:n.36dup

ENST00000583850.5:n.92dup

ENST00000583858.5:n.346dup

ENST00000585203.6:n.523+2dup

NM_000018.3:c.1317dup

NM_001033859.2:c.1251dup

NM_001270447.1:c.1386dup

NM_001270448.1:c.1089dup

NM_001033859.3:c.1251dup

NM_001270447.2:c.1386dup

NM_001270448.2:c.1089dup

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PVS1 PM2_Supporting

PP4

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1317dup (p.Met440fs) variant in ACADVL is a frameshift predicted to cause a premature stop codon in biologically relevant exon 13/20 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 reported as a result of a positive newborn screening for VLCADD (PMID:26385305). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on PVS1, PM2_Supporting.

PVS1

frameshift in exon 13/20

PM2_Supporting

Absent from gnomAD

PP4

2 patients: positive NBS for VLCADD

Approved on: 2022-12-15

Published on: 2022-12-15

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