Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000800024 | SCV000939721 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2024-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 374 of the IVD protein (p.Val374Ala). This variant is present in population databases (rs754600862, gnomAD 0.002%). This missense change has been observed in individual(s) with isovaleric acidemia (PMID: 9665741; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 645855). 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). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000800024 | SCV004198032 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2024-02-19 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000800024 | SCV005380302 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2024-08-23 | criteria provided, single submitter | clinical testing | Variant summary: IVD c.1112T>C (p.Val371Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251462 control chromosomes. c.1112T>C has been reported in the literature in at least one individual affected with Isovaleryl-CoA Dehydrogenase Deficiency (e.g. Mohsen_1998). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 5%-15% of normal activity in vitro (Mohsen_1998). The following publication has been ascertained in the context of this evaluation (PMID: 9665741). ClinVar contains an entry for this variant (Variation ID: 645855). Based on the evidence outlined above, the variant was classified as likely pathogenic. |