Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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). |