Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001924251 | SCV002206984 | pathogenic | Greig cephalopolysyndactyly syndrome; Pallister-Hall syndrome | 2021-02-15 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the GLI3 gene (p.Tyr1254*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 327 amino acids of the GLI3 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Pallister-Hall syndrome (Invitae). This variant disrupts the C-terminus of the GLI3 protein. Other variant(s) that disrupt this region (p.Thr1488Lysfs*23) have been determined to be pathogenic (PMID: 24736735). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. |