Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484478 | SCV000573429 | uncertain significance | not provided | 2017-02-17 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CLN6 gene. The A301G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A301G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues (P297T, P299L, W300R) have been reported in the Human Gene Mutation Database in association with neuronal ceroid lipofuscinosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. However, the A301G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |