Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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). |