Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492599 | SCV000580746 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-04-14 | criteria provided, single submitter | clinical testing | The c.1426dupG pathogenic mutation, located in coding exon 9 of the FLCN gene, results from a duplication of G at nucleotide position 1426, causing a translational frameshift with a predicted alternate stop codon. This alteration was previously seen in a family with Birt-Hogg-Dube syndrome (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun;76(6):1023-33). In addition to the clinical information presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |
| Genetics and Molecular Pathology, |
RCV003447534 | SCV004175208 | pathogenic | Familial spontaneous pneumothorax | 2023-03-02 | criteria provided, single submitter | clinical testing | The FLCN c.1426dup variant is classified as Pathogenic (PVS1, PS4_Supporting, PM2). The gene FLCN c.1426dup variant is located in exon 12/14 and is predicted to cause a shift in the reading frame at codon 476 introducing a premature termination codon 10 amino acids downstream (PVS1). The variant has been reported in one unrelated affected proband with a clinical presentation of Birt-Hogg-Dube Syndrome (PMID: 15852235) (PS4_Supporting). This variant is absent from population databases (PM2). The variant has been reported in dbSNP (rs1131690835) and in the HGMD database: CI051796. It has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 428649). |