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]

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Variant: NM_000018.4(ACADVL):c.1064T>C (p.Ile355Thr)

CA397724272

657040 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 967a4e60-e685-4bca-af80-b944a7929206

Approved on: 2024-09-24

Published on: 2024-10-02

HGVS expressions

NM_000018.4:c.1064T>C

NM_000018.4(ACADVL):c.1064T>C (p.Ile355Thr)

NC_000017.11:g.7222852T>C

CM000679.2:g.7222852T>C

NC_000017.10:g.7126171T>C

CM000679.1:g.7126171T>C

NC_000017.9:g.7066895T>C

NG_007975.1:g.8019T>C

NG_008391.2:g.2199A>G

ENST00000356839.10:c.1064T>C

ENST00000322910.9:c.*1019T>C

ENST00000350303.9:c.998T>C

ENST00000356839.9:c.1064T>C

ENST00000543245.6:c.1133T>C

ENST00000578824.5:n.213T>C

ENST00000582379.1:n.448T>C

ENST00000583858.5:c.93T>C

ENST00000585203.6:n.5T>C

NM_000018.3:c.1064T>C

NM_001033859.2:c.998T>C

NM_001270447.1:c.1133T>C

NM_001270448.1:c.836T>C

NM_001033859.3:c.998T>C

NM_001270447.2:c.1133T>C

NM_001270448.2:c.836T>C

Uncertain Significance

PM2_Supporting

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: c.1064T>C (p.Ile355Thr) in ACADVL is a missense variant predicted to cause substitution of isoleucine by threonine at amino acid 355 (p.Ile355Thr). The highest population minor allele frequency in gnomAD v4.1.0 is 0.000013 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). This variant has been reported in the literature in three patients with an abnormal newborn screen who are apparently heterozygous carriers for the variant (PMID: 26385305), but this information is insufficient to use toward classification. The computational predictor REVEL gives a score of 0.65, which is neither above nor below the thresholds predicting a damaging or benign impact on ACADVL function. Due to limited evidence, this variant is classified as a variant of uncertain significance 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: PM2_Supporting (ACADVL VCEP specifications version 1; approved November 9, 2021).

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.1.0 is 0.000013 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).

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