ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.457-3_457-2delinsGG (rs786204427)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169022 SCV000220169 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2014-03-18 criteria provided, single submitter literature only
Invitae RCV000169022 SCV001402877 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2020-04-07 criteria provided, single submitter clinical testing This sequence change affects acceptor 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 not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with isovaleric acidemia (PMID: 17576084, 22004070, Invitae). This variant is also known as c.457–3_2CA>GG in the literature. ClinVar contains an entry for this variant (Variation ID: 188724). 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: 16602101). For these reasons, this variant has been classified as Pathogenic.

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