Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000692024 | SCV000819831 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg398*) in the IVD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the IVD protein. This variant is present in population databases (rs398123681, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with isovaleric acidemia (PMID: 31707166; Invitae). ClinVar contains an entry for this variant (Variation ID: 571005). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the IVD protein in which other variant(s) (p.Ile405) have been determined to be pathogenic (PMID: 27904153; 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. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV000692024 | SCV001163391 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | criteria provided, single submitter | clinical testing | ||
Knight Diagnostic Laboratories, |
RCV000692024 | SCV001448849 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2018-12-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000692024 | SCV002103665 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-04-11 | criteria provided, single submitter | clinical testing | Variant summary: IVD c.1183C>T (p.Arg395X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251400 control chromosomes. c.1183C>T has been reported in the literature in individuals affected with Isovaleryl-CoA Dehydrogenase Deficiency in the homozyous state (Fisher_2018, Ibarra-Gonzalez_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000692024 | SCV003820841 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2022-11-13 | criteria provided, single submitter | clinical testing |