ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1424C>T (p.Ser475Leu) (rs121908202)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000059623 SCV000790555 likely pathogenic Ceroid lipofuscinosis neuronal 2 2017-03-28 criteria provided, single submitter clinical testing
Invitae RCV000800616 SCV000940342 pathogenic Neuronal ceroid lipofuscinosis 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 475 of the TPP1 protein (p.Ser475Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs121908202, ExAC 0.02%). This variant has been observed in several individuals affected with TPP1-related conditions  (PMID: 10330339, 23266810, 21990111). ClinVar contains an entry for this variant (Variation ID: 68741). This variant has been reported to affect TPP1 protein function (PMID: 20340139). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059623 SCV000091190 not provided Ceroid lipofuscinosis neuronal 2 no assertion provided not provided

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