ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1366C>T (p.Arg456Cys) (rs794727111)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000174652 SCV000225987 uncertain significance not provided 2014-08-20 criteria provided, single submitter clinical testing
Invitae RCV000696055 SCV000824600 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 456 of the ACADVL protein (p.Arg456Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with VLCAD deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 194315). 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. This variant disrupts the p.Arg456 amino acid residue in ACADVL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9973285, 21932095, 26182500, 17206456). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000696055 SCV001365210 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1366C>T (NP_000009.1:p.Arg456Cys) [GRCH38: NC_000017.11:g.7224001C>T] variant in ACADVL gene is interpretated to be Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant has been reported. This variant meets the following evidence codes reported in the ACMG guidelines: PP3

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