ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1220G>C (p.Gly407Ala) (rs904631654)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000544920 SCV000654920 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2020-02-12 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 407 of the ACADVL protein (p.Gly407Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with VLCAD deficiency in a family (PMID: 28755359) and has also been observed in an individual with VLCAD deficiency (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000544920 SCV001365088 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1220G>C (NP_000009.1:p.Gly407Ala) [GRCH38: NC_000017.11:g.7223681G>C] variant in ACADVL gene is interpretated to be Likely pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PM1, PM3, PP3, PP4
GeneDx RCV001591287 SCV001816345 likely pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28755359)
Natera, Inc. RCV000544920 SCV001459251 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2020-09-16 no assertion criteria provided clinical testing

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