Submissions for variant NM_002225.5(IVD):c.1183C>T (p.Arg395Ter) (rs398123681)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000692024	SCV000819831	likely pathogenic	Isovaleryl-CoA dehydrogenase deficiency	2019-10-22	criteria provided, single submitter	clinical testing	This sequence change results in a premature translational stop signal in the IVD gene (p.Arg398*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 29 amino acids of the IVD protein. This variant is present in population databases (rs398123681, ExAC 0.02%). This variant has not been reported in the literature in individuals with IVD-related disease. ClinVar contains an entry for this variant (Variation ID: 571005). Two missense substitutions (p.Arg398Gln, p.Ile405Thr) that lie at this codon or downstream of it have been determined to be likely pathogenic (PMID: 22960500, 24516753, Invitae). This suggests that deletion of this region of the IVD protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics	RCV000692024	SCV001163391	pathogenic	Isovaleryl-CoA dehydrogenase deficiency		criteria provided, single submitter	clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000692024	SCV001448849	likely pathogenic	Isovaleryl-CoA dehydrogenase deficiency	2018-12-17	criteria provided, single submitter	clinical testing