Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003064748 | SCV003445293 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 25 of the PCDH19 protein (p.Leu25Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PCDH19-related conditions (PMID: 21519002). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 2138631). 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 PCDH19 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |