ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.1184G>A (p.Arg395Gln) (rs1477527791)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634868 SCV000756222 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2018-06-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 398 of the IVD protein (p.Arg398Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous or in combination with another IVD variant in several individuals affected with isovaleric acidemia (PMID: 22960500, 24516753, Invitae). This variant is also known as p.Arg395Gln in the literature. 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl RCV000634868 SCV000794294 uncertain significance Isovaleryl-CoA dehydrogenase deficiency 2017-10-05 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000634868 SCV000891671 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2017-12-30 criteria provided, single submitter clinical testing

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