Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Diagnostic Laboratory, |
RCV000239692 | SCV000298089 | likely pathogenic | Birt-Hogg-Dube syndrome | 2016-07-18 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000489596 | SCV000577522 | pathogenic | not provided | 2018-04-25 | criteria provided, single submitter | clinical testing | The c.1528_1530delGAG variant in the FLCN gene is an in-frame deletion that is predicted to eliminate the Glutamic Acid residue at amino acid position 510. This variant has been previously reported in association with Birt-Hogg-Dube syndrome (for examples, see Toro et al., 2008; Benusiglio et al., 2014; Furuya et al., 2017). Functional studies show this variant reduced protein expression and significantly disrupted protein stability (Nahorski et al., 2011). The residue deleted occurs at a position that is conserved across species, but is not located within a known functional domain. Based on currently available evidence, we consider c.1528_1530delGAG to be pathogenic, |
| Ambry Genetics | RCV002392752 | SCV002705174 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-06 | criteria provided, single submitter | clinical testing | The c.1528_1530delGAG pathogenic mutation (also known as p.E510del) is located in coding exon 10 of the FLCN gene. This variant results from an in-frame GAG deletion at nucleotide positions 1528 to 1530. This results in the in-frame deletion of a glutamic acid at codon 510. This alteration has been reported in multiple individuals with personal and/or family history consistent with Birt-Hogg-Dube syndrome (Ambry internal data; Toro JR et al. J. Med. Genet., 2008 Jun;45:321-31; Benusiglio PR et al. Orphanet J Rare Dis, 2014 Oct;9:163; Furuya M et al. Cancer Sci., 2015 Mar;106:315-23; Furuya M et al. Lab. Invest., 2017 Mar;97:343-35). Further, functional analyses of this alteration have shown reduced protein expression and stability (Nahorski MS et al. Hum. Mutat., 2011 Aug;32:921-9). This alteration has demonstrated formation of perinuclear protein aggregates in another functional study (Clausen L et al. PLoS Genet, 2020 Nov;16:e1009187). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The deleted amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |