ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.456+2T>C (rs398123683)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790744 SCV000230191 pathogenic not provided 2012-09-06 criteria provided, single submitter clinical testing
Invitae RCV000178177 SCV000631888 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2017-08-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the IVD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs398123683, ExAC 0.009%). This variant has been reported in the homozygous state in two individuals affected with isovaleric acidemia (PMID: 10677295, 24637313). ClinVar contains an entry for this variant (Variation ID: 94055). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IVD are known to be pathogenic (PMID: 23587913, 10677295, 16602101). For these reasons, this variant has been classified as Pathogenic.

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