Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 | ||
Ce |
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, |
RCV001004404 | SCV002801109 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2022-05-13 | criteria provided, single submitter | clinical testing |