Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492227 | SCV000580736 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-10-20 | criteria provided, single submitter | clinical testing | The c.1014delG pathogenic mutation, located in coding exon 6 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1014, causing a translational frameshift with a predicted alternate stop codon (p.W338Cfs*15). This mutation has previously been reported in a family affected with Birt-Hogg-Dube syndrome (BHDS) (Schmidt LS et al. Am J Hum Genet, 2005 Jun;76:1023-33). In addition, this mutation is also designated as c.1468delG in published literature. 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. |
| Invitae | RCV001390961 | SCV001592869 | pathogenic | Birt-Hogg-Dube syndrome | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp338Cysfs*15) 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 clinical features of Birt-Hogg-Dube syndrome (PMID: 15852235). This variant is also known as c.1468delG. ClinVar contains an entry for this variant (Variation ID: 428643). For these reasons, this variant has been classified as Pathogenic. |