ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.43G>T (p.Gly15Cys) (rs1057524348)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 2019-11-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 15 of the CLN6 protein (p.Gly15Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.