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.515T>C (p.Leu172Pro)

CA397723077

807359 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: dc474177-dbb5-44da-9f5c-3438ece99f91

HGVS expressions

NM_000018.4:c.515T>C

NM_000018.4(ACADVL):c.515T>C (p.Leu172Pro)

NC_000017.11:g.7221575T>C

CM000679.2:g.7221575T>C

NC_000017.10:g.7124894T>C

CM000679.1:g.7124894T>C

NC_000017.9:g.7065618T>C

NG_007975.1:g.6742T>C

NG_008391.2:g.3476A>G

ENST00000356839.10:c.515T>C

ENST00000322910.9:c.*470T>C

ENST00000350303.9:c.449T>C

ENST00000356839.9:c.515T>C

ENST00000543245.6:c.584T>C

ENST00000577191.5:n.592T>C

ENST00000577433.5:n.723T>C

ENST00000577857.5:n.331T>C

ENST00000579286.5:n.696T>C

ENST00000579886.2:c.353T>C

ENST00000580365.1:n.246T>C

ENST00000581378.5:n.233T>C

ENST00000581562.5:n.525-377T>C

ENST00000582166.1:n.496T>C

ENST00000583312.5:c.515T>C

ENST00000583760.1:n.297T>C

NM_000018.3:c.515T>C

NM_001033859.2:c.449T>C

NM_001270447.1:c.584T>C

NM_001270448.1:c.287T>C

NM_001033859.3:c.449T>C

NM_001270447.2:c.584T>C

NM_001270448.2:c.287T>C

Likely Pathogenic

PM2 PM3_Supporting PP4_Moderate PP3

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.515T>C variant in ACADVL is a missense variant predicted to cause substitution of Leucine by Proline at amino acid 172 (p.Leu172Pro). At least one patient with this variant displayed enzyme data which is highly specific for VLCAD. A proband with this variant had residual enzyme activity of 1% of controls (PP4_moderate) PMID 30194637. The computational predictor REVEL gives a score of 0.835, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been detected in at least 2 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. Of those individuals, 1 was compound heterozygous for the variant and a distinct pathogenic variant. The case was not confirmed in trans by parental or other testing methods. The other variant in this case was c.1332+2T>A, 0.5 points were applied to arrive at PM3_supporting. (PMID 30194637). In summary, this variant meets the criteria to be classified as likely 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: PP4, PM2, PP3, PM3 (VCEP specifications version 1; 11/8/2021).

PM2

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PM3_Supporting

This variant has been detected in at least 2 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. Of those individuals, 1 was compound heterozygous for the variant and a distinct pathogenic variant. The case was not confirmed in trans by parental or other testing methods. The other variant in this case was c.1332+2T>A, 0.5 points were applied to arrive at PM3_supporting. (PMID 30194637).

PP4_Moderate

At least one patient with this variant displayed enzyme data which is highly specific for VLCAD. A proband with this variant had residual enzyme activity of 1% of controls. (PP4_moderate) PMID 30194637.

PP3

The computational predictor REVEL gives a score of 0.835, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).

Approved on: 2022-12-14

Published on: 2022-12-14

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.