Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377621 | SCV001575003 | likely pathogenic | Zellweger spectrum disorders | 2020-09-02 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 20 of the PEX1 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 individual(s) with clinical features of Zellweger spectrum disorder (PMID: 9398847). This variant is also known as PBD118 allele b in the literature. 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 PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). 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. |
| Baylor Genetics | RCV003473904 | SCV004203398 | pathogenic | Heimler syndrome 1 | 2021-11-02 | criteria provided, single submitter | clinical testing |