ClinVar

Description

This sequence change creates a premature translational stop signal (p.Trp224Leufs*30) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 184 amino acid(s) of the CLN5 protein. This variant is present in population databases (rs770949806, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 21990111; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.669insC and p.E253X. ClinVar contains an entry for this variant (Variation ID: 56543). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects CLN5 function (PMID: 20052765). This variant disrupts a region of the CLN5 protein in which other variant(s) (p.Lys368Serfs*15) have been determined to be pathogenic (PMID: 20157158, 20960652, 22532218, 25976102; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.