ClinVar

Description

Variant summary: TPP1 c.959T>G (p.Val320Gly) results in a non-conservative amino acid change located in the Peptidase S8/S53 domain (IPR000209) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251222 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.959T>G has been reported in the literature in individual(s) affected with Neuronal Ceroid-Lipofuscinosis (Gardner_2019). This report does 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: 31283065). Two ClinVar submitters have assessed the variant since 2014: both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.