ClinVar Miner

Submissions for variant NM_000018.4(ACADVL):c.1367G>A (p.Arg456His) (rs794727112)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174653 SCV000225988 uncertain significance not provided 2014-11-24 criteria provided, single submitter clinical testing
Counsyl RCV000410559 SCV000487238 likely pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2016-11-02 criteria provided, single submitter clinical testing
Mendelics RCV000410559 SCV001140231 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-05-28 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000410559 SCV001364924 pathogenic Very long chain acyl-CoA dehydrogenase deficiency 2019-11-01 criteria provided, single submitter clinical testing The NM_000018.3:c.1367G>A (NP_000009.1:p.Arg456His) [GRCH38: NC_000017.11:g.7224002G>A] variant in ACADVL gene is interpretated to be Pathogenic based on ACMG guidelines (PMID: 25741868). This variant has been reported in PMID: 9973285; 17206456. This variant meets the following evidence codes reported in the ACMG guidelines: PS1, PS3
Invitae RCV000410559 SCV001380894 uncertain significance Very long chain acyl-CoA dehydrogenase deficiency 2019-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 456 of the ACADVL protein (p.Arg456His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous in an individual affected with VLCAD deficiency (PMID: 17206456), and it has been reported in individuals affected with VLCAD deficiency, however, a second rare variant was not reported (PMID: 9973285, 21932095, 26182500, 17999356). This variant is also known as p.Arg416His in the literature. ClinVar contains an entry for this variant (Variation ID: 194316). 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. 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.

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