ClinVar

Description

Variant summary: CLN8 c.779C>T (p.Pro260Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 251410 control chromosomes, predominantly at a frequency of 0.0026 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in CLN8 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) phenotype (0.00087). c.779C>T has been reported in the literature in two individuals affected with retinal dystrophy, without strong evidence for causality (Kolesnikova_2023). These report(s) do not provide unequivocal conclusions about association of the variant with Neuronal Ceroid-Lipofuscinosis (Batten Disease). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36912596). ClinVar contains an entry for this variant (Variation ID: 205196). Based on the evidence outlined above, the variant was classified as likely benign.