ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.679T>C (p.Cys227Arg)

dbSNP: rs1855595805
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070527 SCV001235778 pathogenic not provided 2021-03-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 863536). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 227 of the TPP1 protein (p.Cys227Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004702627 SCV005202684 uncertain significance not specified 2024-07-10 criteria provided, single submitter clinical testing Variant summary: TPP1 c.679T>C (p.Cys227Arg) results in a non-conservative amino acid change located in the Sedolisin domain (IPR030400) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251410 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.679T>C in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 863536). Based on the evidence outlined above, the variant was classified as uncertain significance.

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