ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.887_888del (p.Pro296fs) (rs753108198)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169392 SCV000220784 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2014-10-10 criteria provided, single submitter literature only
GeneDx RCV000185736 SCV000238664 pathogenic not provided 2014-07-25 criteria provided, single submitter clinical testing The c.887_888delCT mutation has been reported previously in association with VLCAD deficiency (Mathur et al., 1999). The deletion causes a frameshift starting with codon Proline 296, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 17 of the new reading frame, denoted p.Pro296ArgfsX17. This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in ACADVL panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169392 SCV000693968 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing Variant summary: ACADVL c.887_888delCT (p.Pro296ArgfsX17) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250254 control chromosomes (gnomAD). c.887_888delCT has been reported in the literature in individuals affected with Very Long Chain Acyl-CoA Dehydrogenase Deficiency (Hesse_2018, Mathur_1999, Schiff_2013, Wang_2019). These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000169392 SCV001201176 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2020-05-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro296Argfs*17) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs753108198, ExAC 0.01%). This variant has been observed in combination with another ACADVL variant in individuals affected with very long-chain acyl-CoA dehydrogenase deficiency (PMID: 23480858, 30194637). ClinVar contains an entry for this variant (Variation ID: 189008). Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). For these reasons, this variant has been classified as Pathogenic.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000169392 SCV001364908 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.887_888delCT (NP_000009.1:p.Pro296ArgfsTer17) [GRCH38: NC_000017.11:g.7222675_7222676delCT] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 10077518. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3

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