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:c.1968A>C

CA397726277

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 301b1a21-8b88-4b97-89b0-e0a234c089a0

Approved on: 2022-03-08

Published on: 2022-03-08

HGVS expressions

NM_000018.4:c.1968A>C

NC_000017.11:g.7225097A>C

CM000679.2:g.7225097A>C

NC_000017.10:g.7128416A>C

CM000679.1:g.7128416A>C

NC_000017.9:g.7069140A>C

NG_007975.1:g.10264A>C

NG_033038.1:g.14448T>G

ENST00000356839.10:c.1968A>C

ENST00000322910.9:c.*1923A>C

ENST00000350303.9:c.1902A>C

ENST00000356839.9:c.1968A>C

ENST00000542255.6:n.847A>C

ENST00000543245.6:c.2037A>C

ENST00000578033.1:n.393A>C

ENST00000578319.5:n.549A>C

ENST00000578711.1:n.1593A>C

ENST00000578809.5:n.540A>C

ENST00000579425.5:n.1084A>C

ENST00000583848.5:n.334A>C

ENST00000583850.5:n.739A>C

ENST00000583858.5:n.899A>C

NM_000018.3:c.1968A>C

NM_001033859.2:c.1902A>C

NM_001270447.1:c.2037A>C

NM_001270448.1:c.1740A>C

NM_001033859.3:c.1902A>C

NM_001270447.2:c.2037A>C

NM_001270448.2:c.1740A>C

Uncertain Significance

PM2_Supporting PP4 PM4

PP3 PM5 PM3

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.1968A>C variant is predicted to cause a change in the length of the protein due to a stop loss p.(Ter656CysextTer54) (PM4). At least one individual with this variant displayed reduced enzyme assay in leukocytes, which is highly specific for very long chain acyl-CoA dehydrogenase (VLCAD) deficiency (PP4; PMID 27209629). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM4, PP4, PM2_Supporting (VCEP specifications v2.0, approved on 09/16/2021).

PM2_Supporting

Not in gnomAD

PP4

Proband has abnormal newborn screening. Normal acylcarnitine profile was noted, however there was abnormal VLCAD activity in leukocytes.

PM4

Additional 32-aa peptide at the C-terminus via stop-loss variant

PP3

Available computational evidence does not provide predictions for this variant.

PM5

c.1966T>A is at the same codon, but not LP or P

PM3

c.1894C>T is not LP or P

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