Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001825615 | SCV000949421 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 321 of the VRK1 protein (p.Arg321His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200927943, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg321 amino acid residue in VRK1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
Natera, |
RCV001825615 | SCV002093704 | uncertain significance | Pontocerebellar hypoplasia type 1A | 2020-09-09 | no assertion criteria provided | clinical testing |