ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.358G>A (p.Gly120Arg) (rs142761835)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169054 SCV000220214 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2014-04-04 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000153385 SCV000230190 pathogenic not provided 2016-03-16 criteria provided, single submitter clinical testing
GeneDx RCV000153385 SCV000321786 pathogenic not provided 2019-09-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25087612, 28631226, 22004070, 27904153, 22350545, 15486829, 31442447, 28535199)
Fulgent Genetics,Fulgent Genetics RCV000169054 SCV000611202 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV000169054 SCV000631885 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2020-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 123 of the IVD protein (p.Gly123Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs142761835, ExAC 0.01%). This variant has been observed to segregate with isovaleric acidemia in families (PMID: 22350545) and it has been reported as homozygous and in combination with another IVD variant in multiple individuals affected with IVA (PMID: 22350545, 27904153, 22004070, Invitae). This variant is also known as c.358G>A (p.Gly91Arg) in the literature. ClinVar contains an entry for this variant (Variation ID: 167199). 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. This variant disrupts the p.Gly123 amino acid residue in IVD. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 15486829), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000169054 SCV000891669 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2017-12-30 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169054 SCV001163382 pathogenic Isovaleryl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing

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