Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001048645 | SCV001212659 | pathogenic | Birt-Hogg-Dube syndrome | 2019-02-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with FLCN-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile141Hisfs*6) in the FLCN gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV004031520 | SCV005030684 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | The c.420dupC pathogenic mutation, located in coding exon 3 of the FLCN gene, results from a duplication of C at nucleotide position 420, causing a translational frameshift with a predicted alternate stop codon (p.I141Hfs*6). This variant (also sometimes reported as c.875delC in the literature) has been identified in at least one individual with a clinical diagnosis of Birt-Hogg-Dube syndrome (van Steensel MA et al. J Invest Dermatol, 2007 Mar;127:588-93; Leter EM et al. J Invest Dermatol, 2008 Jan;128:45-9; Houweling AC et al. Br J Cancer. 2011 Dec;105(12):1912-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |