ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.500_503dup (p.Phe169fs)

dbSNP: rs1554902020
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478948 SCV000573619 pathogenic not provided 2017-02-20 criteria provided, single submitter clinical testing The c.500_503dupTGGA variant variant in the TPP1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.500_503dupTGGA variant variant causes a frameshift starting with codon Phenylalanine 169, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 20 of the new reading frame, denoted p.Phe169GlyfsX20. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.500_503dupTGGA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.500_503dupTGGA variant as a pathogenic variant.
Invitae RCV000478948 SCV004538881 pathogenic not provided 2023-05-16 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 423868). This premature translational stop signal has been observed in individual(s) with pediatric movement disorders (PMID: 30283815). This sequence change creates a premature translational stop signal (p.Phe169Glyfs*20) 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).

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