ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1417G>A (p.Gly473Arg)

gnomAD frequency: 0.00001  dbSNP: rs121908203
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001854252 SCV002232682 pathogenic not provided 2023-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 473 of the TPP1 protein (p.Gly473Arg). This variant is present in population databases (rs121908203, gnomAD 0.003%). This missense change has been observed in individual(s) with late-infantile neuronal ceroid lipofuscinosis (PMID: 11241479, 11339651). 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: 68740). 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%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005049416 SCV005683677 likely pathogenic Neuronal ceroid lipofuscinosis 2; Autosomal recessive spinocerebellar ataxia 7 2024-06-10 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059622 SCV000091189 not provided Neuronal ceroid lipofuscinosis 2 no assertion provided not provided

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