Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556053 | SCV000658945 | likely pathogenic | Treacher Collins syndrome 1 | 2016-07-22 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 24-26 of the TCOF1 gene. The 5' boundary is likely confined to intron 23. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TCOF1 protein. This variant has not been reported in the literature in individuals with a TCOF1-related disease. Experimental studies have shown that the final 160-190 amino acids of the TCOF1 protein contain nuclear and nucleolar localization signals. Deletion of these residues leads to mislocalization of the protein in cell culture-based assays (PMID: 9811939, 9736782). In summary, this is a novel truncating variant that is expected to disrupt TCOF1 protein localization. However, in the absence of additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. |