Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001231306 | SCV001403823 | uncertain significance | Progressive myoclonic epilepsy | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 29 of the CSTB protein (p.Glu29Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CSTB-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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; 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. |
| Ambry Genetics | RCV002447155 | SCV002679939 | uncertain significance | Inborn genetic diseases | 2018-02-28 | criteria provided, single submitter | clinical testing | The p.E29K variant (also known as c.85G>A), located in coding exon 2 of the CSTB gene, results from a G to A substitution at nucleotide position 85. The glutamic acid at codon 29 is replaced by lysine, an amino acid with similar properties. This amino acid position is not conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |