Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169200 | SCV000220449 | likely pathogenic | Neuronal ceroid lipofuscinosis 2 | 2014-06-23 | criteria provided, single submitter | literature only | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169200 | SCV001339059 | pathogenic | Neuronal ceroid lipofuscinosis 2 | 2020-03-20 | criteria provided, single submitter | clinical testing | Variant summary: TPP1 c.972_979delCTATGGAG (p.Ser324ArgfsX2) 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. The variant allele was found at a frequency of 4e-06 in 251378 control chromosomes (gnomAD). c.972_979delCTATGGAG has been reported in the literature in individuals affected with Late-infantile Neuronal Ceroid-Lipofuscinoses (Sleat_1999). These data indicate that the variant may be associated with disease. At least one publication reports this variant has an impact on protein function and results in <10% of normal TPP1 activity. 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. |
| Invitae | RCV003556210 | SCV004295345 | pathogenic | not provided | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser324Argfs*2) 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 present in population databases (rs778232650, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 10330339). This variant is also known as 4288-4295del. ClinVar contains an entry for this variant (Variation ID: 188850). 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. |