Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003455821 | SCV004176833 | uncertain significance | Very long chain acyl-CoA dehydrogenase deficiency | 2023-11-13 | reviewed by expert panel | curation | The NM_000018.4(ACADVL): c.877C>T variant in ACADVL is a missense variant predicted to cause substitution of histamine by tyrosine at amino acid 293 (p.His293Tyr). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been co-detected with a p.Gly441Asp pathogenic variant in an individual with very long chain acyl CoA dehydrogenase (VLCAD) deficiency with unknown phase confirmation (PM3 point 0.5, PM3_Supporting, PMIDs: 25834949). This patient also displayed reduced enzyme levels (< 20 % of wildtype), which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 25834949). The computational predictor REVEL gives a score of 0.494, which is neither above nor below the thresholds predicting a damaging or benign impact on ACADVL function. Due to conflicting 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, PM3_Supporting, PP4_Moderate (ACADVL VCEP specifications version 1; approved November 9, 2021). |