Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000003748 | SCV000941046 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2018-12-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 53 of the IVD protein (p.Arg53Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs34695403, ExAC 0.009%). This variant has been observed in individuals affected with isovaleric acidemia (PMID: 10677295, Invitae). ClinVar contains an entry for this variant (Variation ID: 3567). This variant is also know as p.Arg21Cys in the literature. This variant has been reported to affect RNA splicing of the IVD gene (PMID:10677295). This variant disrupts the p.Arg53 amino acid residue in IVD. Other variant(s) that disrupt this residue have been observed in individuals with IVD-related conditions (PMID: 17576084, 15486829, 10677295, 19099814, 17027310, 27904153), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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. |
Baylor Genetics | RCV000003748 | SCV001163379 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | criteria provided, single submitter | clinical testing | ||
OMIM | RCV000003748 | SCV000023913 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2000-02-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000003748 | SCV001460257 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |