Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000654887 | SCV000776791 | pathogenic | Treacher Collins syndrome 1 | 2017-12-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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). This variant is a gross deletion of the genomic region encompassing exons 18-26 of the TCOF1 gene. The 5' boundary is likely confined to intron 17. 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 protein product or disrupt mRNA translation. Gross deletion of TCOF1 exons 18-26 has been reported in an individual affected with Treacher Collins syndrome (Invitae). |