Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003806840 | SCV004596939 | pathogenic | Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly1441Valfs*3) in the GLI3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 140 amino acid(s) of the GLI3 protein. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GLI3 protein in which other variant(s) (p.Gln1503*) have been determined to be pathogenic (PMID: 30235038; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with GLI3-related conditions. |