ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.617G>A (p.Arg206His) (rs121908209)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469057 SCV000548744 pathogenic Neuronal ceroid lipofuscinosis 2019-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 206 of the TPP1 protein (p.Arg206His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs121908209, ExAC 0.002%). This variant has been observed in individual(s) with TPP1-related conditions (PMID: 12698559, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68748). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg206 amino acid residue in TPP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30541466, 20340139, 10665500). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001200081 SCV001370944 likely pathogenic not provided 2020-04-01 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059630 SCV000091198 not provided Ceroid lipofuscinosis neuronal 2 no assertion provided not provided
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000469057 SCV000804934 pathogenic Neuronal ceroid lipofuscinosis 2012-08-29 no assertion criteria provided clinical testing

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