Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000535889 | SCV000655672 | pathogenic | Joubert syndrome 23; Short-rib thoracic dysplasia 14 with polydactyly | 2021-09-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this silent change causes aberrant splicing, resulting in the loss of exon 9 and a frameshift in the mRNA (PMID: 26386044). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with features of asphyxiating thoracic dystrophy (Jeune syndrome) and Joubert syndrome (PMID: 26386044), and in combination with another rare variant in an individual affected with Joubert syndrome (PMID: 28497568). In addition, this variant has been observed to segregate with Joubert syndrome in a family (Invitae). This variant is present in population databases (rs780520735, ExAC 0.005%). This sequence change affects codon 330 of the KIAA0586 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the KIAA0586 protein. |