Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000554790 | SCV000655662 | likely pathogenic | Joubert syndrome 23; Short-rib thoracic dysplasia 14 with polydactyly | 2017-12-19 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. This variant has been reported to segregate with Joubert syndrome in a family (Invitae). This variant is present in population databases (rs372841738, ExAC 0.02%). This sequence change falls in intron 22 of the KIAA0586 gene. It does not directly change the encoded amino acid sequence of the KIAA0586 protein, but it affects a nucleotide within the consensus splice site of the intron. |
Gene |
RCV002266986 | SCV002549192 | uncertain significance | not provided | 2022-07-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |