ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.1174C>T (p.Arg392Cys)

gnomAD frequency: 0.00004  dbSNP: rs371427844
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255825 SCV000321787 pathogenic not provided 2016-02-26 criteria provided, single submitter clinical testing The R395C missense variant in the IVD gene has been reported previously using alternative nomenclature in association with isovaleric acidemia (Lin et al., 2007; Sakamoto et al., 2015). When expressed in E. coli, R395C was found to be associated with approximately 1% residual activity compared to wild type (Mohsen et al., 1998). Therefore, we interpret R395C to be a pathogenic variant.
Baylor Genetics RCV001004404 SCV001163389 pathogenic Isovaleryl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000255825 SCV001246421 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
Invitae RCV001004404 SCV001589421 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 395 of the IVD protein (p.Arg395Cys). This variant is present in population databases (rs371427844, gnomAD 0.007%). This missense change has been observed in individuals with isovaleric acidemia (PMID: 9665741, 17027310, 25220015, 26018748). This variant is also known as 1174 C>T (Arg363Cys). ClinVar contains an entry for this variant (Variation ID: 265202). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects IVD function (PMID: 9665741). This variant disrupts the p.Arg395 amino acid residue in IVD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22960500, 25220015, 27904153). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001004404 SCV002801109 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2022-05-13 criteria provided, single submitter clinical testing

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