Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000540760 | SCV000641091 | pathogenic | Dystonia 5; GTP cyclohydrolase I deficiency | 2017-08-17 | criteria provided, single submitter | clinical testing | 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). A different variant affecting this nucleotide (c.344-1G>A) has been determined to be pathogenic (PMID: 8619546). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. This variant has not been reported in the literature in individuals with a GCH1-related disease. 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. |