ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1027G>A (p.Glu343Lys) (rs121908197)

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
Invitae RCV001069102 SCV001234249 pathogenic Neuronal ceroid lipofuscinosis 2019-02-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 343 of the TPP1 protein (p.Glu343Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs121908197, ExAC 0.03%). This variant has been observed to be homozygous and in combination with another TPP1 variant in several individuals affected with late-infantile neuronal ceroid lipofuscinosis (PMID: 10330339). ClinVar contains an entry for this variant (Variation ID: 68734). This variant has been reported to affect TPP1 protein function (PMID:20340139). This variant disrupts the p.Glu343 amino acid residue in TPP1. Other variant(s) that disrupt this residue have been observed in individuals with TPP1-related conditions (PMID:26224725), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059616 SCV000091180 not provided Ceroid lipofuscinosis neuronal 2 no assertion provided not provided

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.