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.896A>T (p.Lys299Met)

CA8337902

932829 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 37e89f02-7ef4-4e15-a98b-55c415cf8d9f

HGVS expressions

NM_000018.4:c.896A>T

NM_000018.4(ACADVL):c.896A>T (p.Lys299Met)

NC_000017.11:g.7222684A>T

CM000679.2:g.7222684A>T

NC_000017.10:g.7126003A>T

CM000679.1:g.7126003A>T

NC_000017.9:g.7066727A>T

NG_007975.1:g.7851A>T

NG_008391.2:g.2367T>A

ENST00000356839.10:c.896A>T

ENST00000322910.9:c.*851A>T

ENST00000350303.9:c.830A>T

ENST00000356839.9:c.896A>T

ENST00000543245.6:c.965A>T

ENST00000578824.5:n.45A>T

ENST00000581378.5:n.614A>T

ENST00000582379.1:n.280A>T

NM_000018.3:c.896A>T

NM_001033859.2:c.830A>T

NM_001270447.1:c.965A>T

NM_001270448.1:c.668A>T

NM_001033859.3:c.830A>T

NM_001270447.2:c.965A>T

NM_001270448.2:c.668A>T

Likely Pathogenic

PM3 PM2_Supporting PP4_Moderate PP3

PM5

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.896A>T (p.Lys299Met) variant in ACADVL has been reported in the literature in patients with VLCAD deficiency and elevated acylcarnitine (PP4_moderate; PMID: 16982043, 35281659). The variant has also been detected in compound heterozygote with pathogenic variant p.Val283Ala (PM3; PMID: 35281659). Three missense variants (p.Lys299Asn, p.Lys299Arg, p.Lys299Glu; PMIDs: 9973285, 31737040, 33150772) in the same codon have also been reported for VLCAD deficiency. This variant is absent from gnomAD population database v2.1.1(PM2_Supporting) and the computational predictor REVEL gives a score of 0.963, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on (PP4_moderate, PM3, PM2_Supporting, PP3).

PM3

Found with L502Q - unknown phase. not classified by Clingen Found with p.V283A in two patients & p.R632C (not classified by Clingen) Points = 1

PM2_Supporting

absent

PP4_Moderate

Elevated C14:0, Enzyme activity 16% of control (used patient derived material) C14:1 > 1.0uM and assertion of VLCADD (patient material)

PP3

0.963 (>0.75)

PM5

Other missense of this codon (K299N/R/E). None classified by Clingen.

Approved on: 2023-06-13

Published on: 2023-06-13

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