Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169054 | SCV000220214 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2014-04-04 | criteria provided, single submitter | literature only | |
EGL Genetic Diagnostics, |
RCV000153385 | SCV000230190 | pathogenic | not provided | 2016-03-16 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000153385 | SCV000321786 | pathogenic | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | The G123R variant has previously been reported in association with isovaleric acidemia in several unrelated families of South African descent; affected individuals were homozygous for G123R and all patients were found to have undetectable residual isovaleryl-CoA dehydrogenase activity in fibroblasts (Dercksen et al., 2012). The G123R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G123R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, we interpret G123R to be a pathogenic variant. |
Fulgent Genetics, |
RCV000169054 | SCV000611202 | likely pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2017-05-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000169054 | SCV000631885 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2019-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 123 of the IVD protein (p.Gly123Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs142761835, ExAC 0.01%). This variant has been observed to segregate with isovaleric acidemia in families (PMID: 22350545) and it has been reported as homozygous and in combination with another IVD variant in multiple individuals affected with IVA (PMID: 22350545, 27904153, 22004070, Invitae). This variant is also known as c.358G>A (p.Gly91Arg) in the literature. ClinVar contains an entry for this variant (Variation ID: 167199). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant disrupts the p.Gly123 amino acid residue in IVD. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 15486829), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Department of Genetics, |
RCV000169054 | SCV000891669 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | 2017-12-30 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000169054 | SCV001163382 | pathogenic | Isovaleryl-CoA dehydrogenase deficiency | criteria provided, single submitter | clinical testing |