ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.790C>T (p.Gln264Ter)

dbSNP: rs1405952769
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002266274 SCV002548007 pathogenic Neuronal ceroid lipofuscinosis 2022-05-02 criteria provided, single submitter clinical testing Variant summary: TPP1 c.790C>T (p.Gln264X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251370 control chromosomes. c.790C>T has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) or related disorders. These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003560903 SCV004295346 pathogenic not provided 2023-11-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln264*) in the TPP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TPP1 are known to be pathogenic (PMID: 10330339). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal recessive neuronal ceroid lipofuscinosis (PMID: 26143525). ClinVar contains an entry for this variant (Variation ID: 1696130). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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