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]
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Variant: NM_000018.4(ACADVL):c.1357C>T (p.Arg453Ter)

CA274997

194317 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 18582346-288f-4289-903c-5939c2d10243
Approved on: 2022-12-15
Published on: 2022-12-15

HGVS expressions

NM_000018.4:c.1357C>T
NM_000018.4(ACADVL):c.1357C>T (p.Arg453Ter)
NC_000017.11:g.7223992C>T
CM000679.2:g.7223992C>T
NC_000017.10:g.7127311C>T
CM000679.1:g.7127311C>T
NC_000017.9:g.7068035C>T
NG_007975.1:g.9159C>T
NG_008391.2:g.1059G>A
NG_033038.1:g.15553G>A
ENST00000356839.10:c.1357C>T
ENST00000322910.9:c.*1312C>T
ENST00000350303.9:c.1291C>T
ENST00000356839.9:c.1357C>T
ENST00000542255.6:n.215C>T
ENST00000543245.6:c.1426C>T
ENST00000578711.1:n.488C>T
ENST00000579425.5:n.473C>T
ENST00000579546.1:n.194C>T
ENST00000579894.5:n.68C>T
ENST00000583074.5:n.76C>T
ENST00000583850.5:n.132C>T
ENST00000583858.5:n.386C>T
ENST00000585203.6:n.548C>T
NM_000018.3:c.1357C>T
NM_001033859.2:c.1291C>T
NM_001270447.1:c.1426C>T
NM_001270448.1:c.1129C>T
NM_001033859.3:c.1291C>T
NM_001270447.2:c.1426C>T
NM_001270448.2:c.1129C>T
More

Pathogenic

Met criteria codes 3
PM3 PVS1 PM2_Supporting
Not Met criteria codes 1
PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The NM_000018.4(ACADVL):c.1357C>T (p.Arg453Ter) variant in ACADVL is a nonsense predicted to cause a premature stop codon in biologically relevant exon 14/20 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 detected and confirmed in-trans with the pathogenic c.1349G>A (p.R450H) in a patient with VLCAD-deficiency (PM3, PMID:33150772). This variant was also reported in one patient with a positive newborn screen for VLCAD-deficiency (PMID:26385305). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003 in the Latino population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting (PM2_Supporting). The ACADVL Variant Curation Expert Panel VCEP classified the variant as pathogenic based on PVS1,PM3,PM2_Supporting.
Met criteria codes
PM3
Family 4 ,table S1: Confirmed in trans with pathogenic p.R450H (9 family-study for VLCAD-deficiency. ) Points=1
PVS1
stop codon exon 14/20
PM2_Supporting
1 allele in gnomAD (MAF=0.000003978)
Not Met criteria codes
PP4
1 allele from a large study for VLCADD/positive NBS
Curation History
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