Variant: NM_000018.4(ACADVL):c.1103A>C (p.Gln368Pro)

CA8337965

439360 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: d71d6390-5664-4b34-bad8-622817b3c626

Approved on: 2024-09-10

Published on: 2024-12-18

HGVS expressions

NM_000018.4:c.1103A>C
NM_000018.4(ACADVL):c.1103A>C (p.Gln368Pro)
NC_000017.11:g.7223158A>C
CM000679.2:g.7223158A>C
NC_000017.10:g.7126477A>C
CM000679.1:g.7126477A>C
NC_000017.9:g.7067201A>C
NG_007975.1:g.8325A>C
NG_008391.2:g.1893T>G
ENST00000356839.10:c.1103A>C
ENST00000322910.9:c.*1058A>C
ENST00000350303.9:c.1037A>C
ENST00000356839.9:c.1103A>C
ENST00000543245.6:c.1172A>C
ENST00000578579.2:n.52A>C
ENST00000578824.5:n.519A>C
ENST00000579425.5:n.127A>C
ENST00000582379.1:n.754A>C
ENST00000583858.5:c.132A>C
ENST00000585203.6:n.311A>C
NM_000018.3:c.1103A>C
NM_001033859.2:c.1037A>C
NM_001270447.1:c.1172A>C
NM_001270448.1:c.875A>C
NM_001033859.3:c.1037A>C
NM_001270447.2:c.1172A>C
NM_001270448.2:c.875A>C

Uncertain Significance

• Met criteria codes: PP3 PM2_Supporting

• Not Met criteria codes: PP4

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.1103A>C (NM_000018.4) variant in ACADVL is a missense variant predicted to cause substitution of glutamine by proline at amino acid 368 (p.Gln368Pro). Several individuals with this variant were identified by newborn screen or were identified in individuals without additional laboratory data to support affected status, so this information is insufficient to use toward classification (PMID: 26385305, 31031081). This variant is only detected on one allele in gnomAD v2.1.1, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.98, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant meets the criteria to be classified as a variant of uncertain significance 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: PM2_Supporting, PP3 (ACADVL VCEP specifications version 1; approved November 9, 2021).

Met criteria codes

• PP3: The computational predictor REVEL gives a score of 0.98, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).
• PM2_Supporting: This variant is only detected on one allele in gnomAD v2.1.1, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).

Not Met criteria codes

• PP4: Several individuals with this variant were identified by newborn screen or were identified in individuals without additional laboratory data to support affected status, so this information is insufficient to use toward classification (PMID: 26385305, 31031081).