ClinVar Miner

Submissions for variant NM_002225.5(IVD):c.550+1G>A (rs377147994)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413513 SCV000490570 pathogenic not provided 2016-11-23 criteria provided, single submitter clinical testing The c.559+1 G>A splice site variant in the IVD gene destroys the canonical splice donor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation.\Although this variant has not been previously reported to our knowledge, it is interpreted to be a pathogenic variant.
Baylor Genetics RCV000984189 SCV001163384 pathogenic Isovaleryl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing
Invitae RCV000984189 SCV001222259 pathogenic Isovaleryl-CoA dehydrogenase deficiency 2019-12-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 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 (rs377147994, ExAC 0.01%). This variant has been observed in an individual with clinical features of isovaleric acidemia (Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 372389). 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.
Counsyl RCV000984189 SCV001132236 likely pathogenic Isovaleryl-CoA dehydrogenase deficiency 2014-01-02 no assertion criteria provided clinical testing

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