Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000634832 | SCV000756176 | pathogenic | Dystonia 5; GTP cyclohydrolase I deficiency | 2017-10-05 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with dystonia (PMID: 8619546, Invitae). Experimental studies have shown that this acceptor splice site variant leads to skipping of exon 2 and reduced mRNA expresssion (PMID: 8619546). 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). For these reasons, this variant has been classified as Pathogenic. |