Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685087 | SCV000812559 | uncertain significance | Non-ketotic hyperglycinemia | 2018-02-05 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with glycine at codon 6 of the GCSH protein (p.Val6Gly). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glycine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with GCSH-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |