Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001377063 | SCV001574295 | likely pathogenic | Bardet-Biedl syndrome | 2018-03-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 of the TTC8 gene. It does not directly change the encoded amino acid sequence of the TTC8 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with Bardet-Biedl syndrome (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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. 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. |