Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000634832 | SCV000756176 | pathogenic | Dystonia 5; GTP cyclohydrolase I deficiency | 2017-09-24 | criteria provided, single submitter | clinical testing | This variant has been reported in individuals affected with dystonia (PMID: 8619546, Invitae). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GCH1 are known to be pathogenic (PMID: 19491146). Experimental studies have shown that this acceptor splice site variant leads to skipping of exon 2 and reduced mRNA expresssion (PMID: 8619546). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 1 of the GCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Unidad de Genómica Garrahan, |
RCV003483695 | SCV004232379 | pathogenic | Dystonic disorder | 2024-01-11 | criteria provided, single submitter | clinical testing |