Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000433075 | SCV000535288 | uncertain significance | not provided | 2017-07-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CLN6 gene. The G15C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G15C variant is not observed in large population cohorts; however, data available are limited (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G15C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001052469 | SCV001216681 | uncertain significance | Neuronal ceroid lipofuscinosis | 2022-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 15 of the CLN6 protein (p.Gly15Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 392077). 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: "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. |