Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000800024 | SCV000939721 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2023-10-05 | 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; Invitae). 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 |