ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1397T>G (p.Val466Gly) (rs398122959)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000542832 SCV000628900 pathogenic Neuronal ceroid lipofuscinosis 2017-10-19 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 466 of the TPP1 protein (p.Val466Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autosomal recessive spinocerebellar ataxia in 2 families, and was observed on the opposite chromosome from a pathogenic variant (PMID: 23418007). Affected individuals in these families had TPP1 enzyme activity below the reference range (PMID: 23418007). ClinVar contains an entry for this variant (Variation ID: 89086). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000074609 SCV000108698 pathogenic Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia 2013-05-01 no assertion criteria provided literature only

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