ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.605C>T (p.Pro202Leu)

dbSNP: rs121908205
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000059629 SCV000220406 likely pathogenic Neuronal ceroid lipofuscinosis 2 2014-06-13 criteria provided, single submitter literature only
Invitae RCV001854254 SCV002247008 pathogenic not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 202 of the TPP1 protein (p.Pro202Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 11589012; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68747). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TPP1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects TPP1 function (PMID: 20340139). For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059629 SCV000091196 not provided Neuronal ceroid lipofuscinosis 2 no assertion provided not provided

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