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.619T>C (p.Ser207Pro)

CA8337769

551588 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a8d50bf8-d177-4bc2-b8b3-245d4c748998

HGVS expressions

NM_000018.4:c.619T>C

NM_000018.4(ACADVL):c.619T>C (p.Ser207Pro)

NC_000017.11:g.7221679T>C

CM000679.2:g.7221679T>C

NC_000017.10:g.7124998T>C

CM000679.1:g.7124998T>C

NC_000017.9:g.7065722T>C

NG_007975.1:g.6846T>C

NG_008391.2:g.3372A>G

ENST00000356839.10:c.619T>C

ENST00000322910.9:c.*574T>C

ENST00000350303.9:c.553T>C

ENST00000356839.9:c.619T>C

ENST00000543245.6:c.688T>C

ENST00000577191.5:n.696T>C

ENST00000577857.5:n.435T>C

ENST00000579286.5:n.800T>C

ENST00000579886.2:c.457T>C

ENST00000580365.1:n.350T>C

ENST00000581378.5:c.337T>C

ENST00000581562.5:n.525-273T>C

ENST00000583312.5:c.619T>C

ENST00000583760.1:n.401T>C

NM_000018.3:c.619T>C

NM_001033859.2:c.553T>C

NM_001270447.1:c.688T>C

NM_001270448.1:c.391T>C

NM_001033859.3:c.553T>C

NM_001270447.2:c.688T>C

NM_001270448.2:c.391T>C

Likely Pathogenic

PP4_Moderate PM2 PP3 PM3_Strong

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL): c.619T>C (p.Ser207Pro) variant is a missense variant predicted to cause substitution of serine by proline at amino acid 207. At least two individuals with this variant displayed a newborn screen consistent with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency as well as follow-up acylcarnitine testing showing increased C14:1 acylcarnitines, which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 26927351). This individual was compound heterozygous for this variant and a distinct pathogenic or likely pathogenic variant confirmed in trans by parental testing (PM3_Strong). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.79, 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 likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting, PM3_Strong, PP3, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021).

PP4_Moderate

At least one patient with this variant displayed newborn screen consistent with very long chain acyl-CoA dehydrogenase (VLCAD) deficiency as well as follow-up acylcarnitine testing showing increased C14:1 acylcarnitines, which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 26927351).

PM2

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

PP3

The computational predictor REVEL gives a score of 0.79, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).

PM3_Strong

Confirmed in trans by parental testing to c.1770_1773del (curated by VCEP as pathogenic; cdot nomenclature confirmed by Sanger sequencing in figure 1)

Approved on: 2024-02-27

Published on: 2024-02-27

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