Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000807445 | SCV000947498 | likely pathogenic | Haim-Munk syndrome; Periodontitis, aggressive 1; Papillon-Lefèvre syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CTSC protein function. ClinVar contains an entry for this variant (Variation ID: 651983). This missense change has been observed in individuals with clinical features of Papillon-Lef√®vre syndrome (PMID: 11106356; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine with asparagine at codon 304 of the CTSC protein (p.Tyr304Asn). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and asparagine. |