ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.395T>C (p.Val132Ala)

dbSNP: rs1555360034
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497630 SCV000589526 likely pathogenic not provided 2021-09-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001857005 SCV002251191 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2021-09-04 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 132 of the GCH1 protein (p.Val132Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 431944). This variant has not been reported in the literature in individuals affected with GCH1-related conditions. This variant is not present in population databases (ExAC no frequency).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.