Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Diagnostic Laboratory, |
RCV000239633 | SCV000298062 | pathogenic | Birt-Hogg-Dube syndrome | 2016-07-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000239633 | SCV000549454 | pathogenic | Birt-Hogg-Dube syndrome | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln285*) in the FLCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Birt-Hogg-Dubé syndrome (PMID: 24393238). ClinVar contains an entry for this variant (Variation ID: 253239). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001582803 | SCV001819932 | pathogenic | not provided | 2021-01-07 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 26763815, 23067074, 29357828, 24393238) |
| Ambry Genetics | RCV002446482 | SCV002676763 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-07-09 | criteria provided, single submitter | clinical testing | The p.Q285* pathogenic mutation (also known as c.853C>T), located in coding exon 5 of the FLCN gene, results from a C to T substitution at nucleotide position 853. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This alteration was identified in a 52-year-old Caucasian male with innumerable facial fibrofolliculomas and trichodiscomas, a history of bilateral spontaneous pneumothoraces, and a unilateral oncocytic/ chromophobe renal tumor with low-grade renal cell carcinoma features; his son reportedly had similar facial skin lesions and history of recurrent pneumothorax (Ge L et al. Med. J. Aust. 2016 Jan;204:28-9). This alteration was also identified in a cohort of Asian Birt-Hogg-Dube syndrome patients (Kumasaka T et al. Histopathology. 2014 Jul;65:100-10). In addition to the clinical data presented in the literature, 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. |
| Division of Respiratory Medicine of Juntendo University, |
RCV000239633 | SCV004032408 | pathogenic | Birt-Hogg-Dube syndrome | 2023-07-01 | no assertion criteria provided | clinical testing |