ClinVar Miner

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

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469057 SCV000548744 likely pathogenic Neuronal ceroid lipofuscinosis 2018-07-06 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 reported in combination with other TPP1 variants in individuals affected with neuronal ceroid lipofuscinosis 2 (CLN2) (PMID: 12698559 [in Russian], Invitae). ClinVar contains an entry for this variant (Variation ID: 68748). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
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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