ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.428_467del (p.Gly143fs) (rs758144859)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480851 SCV000572612 pathogenic not provided 2018-04-18 criteria provided, single submitter clinical testing The c.428_467del40 variant in the ACADVL gene has been reported previously in association with very long chain acyl-coA dehydrogenase (VLCAD) deficiency (Miller et al. 2015). The c.428_467del40 variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.428_467del40 variant causes a frameshift starting with codon Glycine 143, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 61 of the new reading frame, denoted p.Gly142AlafsX61. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret c.428_467del40 to be a pathogenic variant.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000671508 SCV001364959 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.428_467del40 (NP_000009.1:p.Gly143AlafsTer61) [GRCH38: NC_000017.11:g.7221009_7221048del] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PVS1, PS3
Invitae RCV000671508 SCV001579730 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2020-02-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly143Alafs*61) in the ACADVL gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual with a positive newborn screening result for ACADVL-related disease (PMID: 26385305) ClinVar contains an entry for this variant (Variation ID: 422995). Loss-of-function variants in ACADVL are known to be pathogenic (PMID: 9973285, 11590124). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000671508 SCV000796491 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2017-12-18 no assertion criteria provided clinical testing

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