Submissions for variant NM_000391.4(TPP1):c.1376A>C (p.Tyr459Ser)

dbSNP: rs864309505

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine	RCV000202601	SCV004047314	likely pathogenic	Neuronal ceroid lipofuscinosis 2		criteria provided, single submitter	clinical testing	The missense variant c.1376A>C (p.Tyr459Ser) in TPP1 gene has been previously reported in patients with Neuronal Ceroid Lipofuscinosis type-2 (NCL2) disease (Sheth et al. 2018). The p.Tyr459Ser variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Likely Pathogenic. The amino acid Tyr at position 459 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Tyr459Ser in TPP1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000202601	SCV000257502	likely pathogenic	Neuronal ceroid lipofuscinosis 2	2015-08-07	no assertion criteria provided	clinical testing	Variant c.1376A>C(p.Y459S) was found to be pathogenic by online software, including MutationTaster, SIFT and Polyphen.