Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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 |