Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000213153 | SCV000273532 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-01-27 | criteria provided, single submitter | clinical testing | The c.59delT pathogenic mutation, located in coding exon 1 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 59, causing a translational frameshift with a predicted alternate stop codon (p.F20Sfs*35). This mutation (also reported as c.513delT) has been reported families with Birt-Hogg-Dubé syndrome (Schmidt LS, Am. J. Hum. Genet. 2005 Jun; 76(6):1023-33; Skolnik K et al. Respir Res, 2016 Feb;17:22). 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. |
Genomic Diagnostic Laboratory, |
RCV000239668 | SCV000298037 | pathogenic | Birt-Hogg-Dube syndrome | 2016-07-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000256007 | SCV000321647 | pathogenic | not provided | 2021-11-19 | criteria provided, single submitter | clinical testing | Frameshift 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 at a significant frequency in large population cohorts (Lek 2016); Also known as c.513delT or c.514delT; This variant is associated with the following publications: (PMID: 21937013, 18234728, 15852235, 19802896, 26928018, 21398229, 22864127, 27780965, 29357828) |
Invitae | RCV000239668 | SCV004298124 | pathogenic | Birt-Hogg-Dube syndrome | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Phe20Serfs*35) 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: 26928018). ClinVar contains an entry for this variant (Variation ID: 230104). For these reasons, this variant has been classified as Pathogenic. |