ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.767A>G (p.Asp256Gly) (rs143781303)

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 RCV000187106 SCV000240681 pathogenic not provided 2013-06-27 criteria provided, single submitter clinical testing p.Asp256Gly (GAC>GGC): c.767 A>G in exon 7 of the CLN6 gene (NM_017882.2)The Asp256Gly missense change was previously reported as a homozygous mutation in multiple individuals from the same family with teenage-onset progressive myoclonic epilepsy (Andrade et al., 2012). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a negatively charged Aspartic acid residue is replaced by an uncharged, non-polar Glycine residue. It alters a conserved position in the cytoplasmic loop between the sixth and seventh transmembrane domains of the protein, and other missense mutations have been reported in this region of the protein. The variant is found in EPILEPSY panel(s).
Invitae RCV001037728 SCV001201156 uncertain significance Neuronal ceroid lipofuscinosis 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 256 of the CLN6 protein (p.Asp256Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs143781303, ExAC 0.01%). This variant has not been reported in the literature in individuals with CLN6-related conditions. ClinVar contains an entry for this variant (Variation ID: 205177). 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: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Asp256 amino acid residue in CLN6. Other variant(s) that disrupt this residue have been observed in individuals with CLN6-related conditions (PMID: 22883287, 24102492), which suggests that this may be a clinically significant amino acid residue. 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.