Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000540901 | SCV000631891 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-09-21 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with isovaleric acidemia (PMID: 35782626; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 286 of the IVD protein (p.Glu286Gly). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 459931). This variant is also known as c.848A>G, (p.Glu283Gly). |
| Natera, |
RCV000540901 | SCV001461294 | uncertain significance | Isovaleryl-CoA dehydrogenase deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |