Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001876290 | SCV002188194 | pathogenic | not provided | 2021-09-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val466Glyfs*21) 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 (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 967557). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001242500 | SCV002819601 | likely pathogenic | Neuronal ceroid lipofuscinosis | 2022-12-16 | criteria provided, single submitter | clinical testing | Variant summary: TPP1 c.1397_1408delinsGACACCGA (p.Val466GlyfsX21) 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 and associated with Neuronal Ceroid-Lipofuscinosis in HGMD. The variant was absent in 282854 control chromosomes. To our knowledge, no occurrence of c.1397_1408delinsGACACCGA in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |