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]
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_000018.4(ACADVL):c.1843C>T (p.Arg615Ter)

CA16608642

379145 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: b254f4fe-4863-47be-9ea1-0becf7133894
Approved on: 2022-12-15
Published on: 2022-12-15

HGVS expressions

NM_000018.4:c.1843C>T
NM_000018.4(ACADVL):c.1843C>T (p.Arg615Ter)
NC_000017.11:g.7224972C>T
CM000679.2:g.7224972C>T
NC_000017.10:g.7128291C>T
CM000679.1:g.7128291C>T
NC_000017.9:g.7069015C>T
NG_007975.1:g.10139C>T
NG_008391.2:g.79G>A
NG_033038.1:g.14573G>A
ENST00000356839.10:c.1843C>T
ENST00000322910.9:c.*1798C>T
ENST00000350303.9:c.1777C>T
ENST00000356839.9:c.1843C>T
ENST00000542255.6:n.722C>T
ENST00000543245.6:c.1912C>T
ENST00000578033.1:n.268C>T
ENST00000578319.5:n.424C>T
ENST00000578711.1:n.1468C>T
ENST00000578809.5:n.415C>T
ENST00000579425.5:n.959C>T
ENST00000579546.1:n.578C>T
ENST00000583848.5:n.209C>T
ENST00000583850.5:n.614C>T
ENST00000583858.5:n.774C>T
NM_000018.3:c.1843C>T
NM_001033859.2:c.1777C>T
NM_001270447.1:c.1912C>T
NM_001270448.1:c.1615C>T
NM_001033859.3:c.1777C>T
NM_001270447.2:c.1912C>T
NM_001270448.2:c.1615C>T
More

Likely Pathogenic

Met criteria codes 4
PM2_Supporting PM3 PP4_Moderate PVS1_Moderate
Not Met criteria codes 1
PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.1843C>T (p.Arg615Ter) variant in ACADVL is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove about 10% of the protein from the C-terminus (PVS1_Moderate; PMIDs 9973285, 11590124). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was also detected and confirmed in-trans with the likely pathogenic p.Glu130del in a patient with VLCAD-deficiency (PM3, PMID:10431122). The patient with this variant also displayed elevated C14:1, which is highly specific for Very long chain acyl coenzyme A dehydrogenase deficiency (PP4_moderate, PMID:10431122). The ACADVL Variant Curation Expert Panel VCEP classified the variant as likely pathogenic based on: PVS1_moderate+PM3+PM2_supporting+PP4_moderate.
Met criteria codes
PM2_Supporting
Not in gnomAD
PM3
This variant has been seen confirmed in-trans with two different variants, one of which (p.E130del) is almost certainly pathogenic. FOLLOW UP WHEN COMPLETE E130del approved likely pathogenic
PP4_Moderate
Elevated C14:1 levels of 4.38 µmol/L is significantly higher than the required 1.0 µmol/L and has confirmatory testing, which meets Moderate criteria
PVS1_Moderate
Although this variant leads to a termination codon (p.Arg615Ter), this falls within the final coding exon and is not predicted to undergo NMD. Although there could be some impact with inner mitochondrial membrane interaction, the function of the lost domains are not known to be critical and <10% of the protein is removed due to the termination.
Not Met criteria codes
PM5
Seen in the same codon as p.Arg615Gln, however this variant meets BA1 and is therefore classified as bengin.
Curation History
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.
¤ Powered by BCM's Genboree.