Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003764534 | SCV004570768 | pathogenic | Haim-Munk syndrome; Periodontitis, aggressive 1; Papillon-Lefèvre syndrome | 2023-07-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln286*) in the CTSC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 178 amino acid(s) of the CTSC protein. This variant is present in population databases (rs104894209, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Papillon-Lefevre syndrome (PMID: 10593994). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 7292). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CTSC protein in which other variant(s) (p.Gln286Arg) have been determined to be pathogenic (PMID: 10662807). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000007715 | SCV000027916 | pathogenic | Papillon-Lefèvre syndrome | 1999-12-01 | no assertion criteria provided | literature only |