ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1093T>C (p.Cys365Arg) (rs119455953)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001248011 SCV001421470 pathogenic Neuronal ceroid lipofuscinosis 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 365 of the TPP1 protein (p.Cys365Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another TPP1 variant in an individual affected with late-infantile neuronal ceroid lipofuscinosis (PMID: 10330339). This gene is also known as CLN2, and this variant is also known as 4654T>C in the literature. ClinVar contains an entry for this variant (Variation ID: 2641). This variant has been reported to affect TPP1 protein function (PMID: 20340139). This variant disrupts the p.Cys365 amino acid residue in TPP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10330339, 9788728, 26075876). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002760 SCV000022918 pathogenic Ceroid lipofuscinosis neuronal 2 1997-09-19 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000002760 SCV000091182 not provided Ceroid lipofuscinosis neuronal 2 no assertion provided not provided

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