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.342+1G>C

CA397722627

474896 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7298dcb2-ce41-467d-91be-c41644471556

Approved on: 2022-02-07

Published on: 2022-04-06

HGVS expressions

NM_000018.4:c.342+1G>C

NM_000018.4(ACADVL):c.342+1G>C

NC_000017.11:g.7220831G>C

CM000679.2:g.7220831G>C

NC_000017.10:g.7124150G>C

CM000679.1:g.7124150G>C

NC_000017.9:g.7064874G>C

NG_007975.1:g.5998G>C

NG_008391.2:g.4220C>G

ENST00000356839.10:c.342+1G>C

ENST00000322910.9:c.*297+1G>C

ENST00000350303.9:c.276+1G>C

ENST00000356839.9:c.342+1G>C

ENST00000543245.6:c.411+1G>C

ENST00000577191.5:n.419+1G>C

ENST00000577433.5:n.550+1G>C

ENST00000577857.5:n.293+1G>C

ENST00000579286.5:n.523+1G>C

ENST00000579886.2:c.202-114G>C

ENST00000580365.1:n.73+1G>C

ENST00000581378.5:n.41+1G>C

ENST00000581562.5:n.389+1G>C

ENST00000582056.5:n.433G>C

ENST00000582166.1:n.231G>C

ENST00000582356.5:n.542G>C

ENST00000583312.5:c.342+1G>C

ENST00000584103.5:c.342+1G>C

NM_000018.3:c.342+1G>C

NM_001033859.2:c.276+1G>C

NM_001270447.1:c.411+1G>C

NM_001270448.1:c.114+1G>C

NM_001033859.3:c.276+1G>C

NM_001270447.2:c.411+1G>C

NM_001270448.2:c.114+1G>C

Pathogenic

PP4_Moderate PVS1 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.342+1G>C variant in ACADVL occurs within the canonical splice donor site of intron 5. It is predicted to cause skipping of biologically-relevant-exon 5, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Moderate). This variant is reported in at least one patient with severe hypoglycemia and postmortem C14:1 measurement of 1.35uM (PP4, PMID: 20107901). In addition, this patient carried the p.Val283Ala mutation. 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, PM2_supporting, PP4_Moderate).

PP4_Moderate

Noted from study: "We present a patient who died as a result of fatal hypoglycemia at 38 h of life before diagnosis of VLCADD could be established by newborn screening." Evaluated C14:1 =1.35, C14=3.17 from postmortem blood.

PVS1

Intron 5 canonical donor splice site

PM2_Supporting

Absent from gnomAD

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