ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.1205T>C (p.Ile402Thr) (rs763422682)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000634867 SCV000796030 uncertain significance Isovaleryl-CoA dehydrogenase deficiency 2017-12-04 criteria provided, single submitter clinical testing
Invitae RCV000634867 SCV000756221 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2018-06-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 405 of the IVD protein (p.Ile405Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs763422682, ExAC 0.009%). This variant has been reported in combination with a second variant in the IVD gene in individuals affected with isovaleric acidemia (PMID: 27904153). 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 and their clinical significance is uncertain. 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.

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