Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556904 | SCV000632817 | pathogenic | Birt-Hogg-Dube syndrome | 2017-05-05 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing the last 102 nucleotides of exon 13 through the last exon 14, and the additional nucleotides in the 3'UTR of the FLCN gene (c.1437_*921del). While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product. This particular deletion has not been reported in the literature in individuals with a FLCN-related disease. This gross deletion is expected to affect the C-terminal FNIP1/FNIP2 interaction domain including the minimal interaction region (residues 517-579), which is required to influence mTOR signaling pathway (PMID: 26334087, 17028174, 18403135, 18663353). Different truncations affecting downstream of this variant (deletion of exon 14, p.Arg527*) has been determined to be pathogenic (PMID: 24393238, 25807935, 27229674, Invitae). This suggests that deletion of this region of the FLCN protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |