Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001939420 | SCV002231147 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2021-10-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the IVD protein in which other variant(s) (p.Arg53His) have been determined to be pathogenic (PMID: 2063866, 10677295, 31442447; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that this variant results in skipping of exon 2, but is expected to preserve the integrity of the reading-frame (PMID: 10677295). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has been observed in individual(s) with IVD-related conditions (PMID: 9665741). This sequence change replaces aspartic acid with asparagine at codon 40 of the IVD protein (p.Asp40Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. |
| Baylor Genetics | RCV001939420 | SCV004198017 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-08-20 | criteria provided, single submitter | clinical testing |