Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519187 | SCV000617531 | pathogenic | not provided | 2017-09-01 | criteria provided, single submitter | clinical testing | The Q217X nonsense variant in the FLCN gene has been reported previously in at least one individual with features consistent with Birt-Hogg-Dube syndrome (Kluger et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q217X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Based on currently available evidence, we consider Q217X to be pathogenic. |
Ambry Genetics | RCV002367730 | SCV002659246 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-11-30 | criteria provided, single submitter | clinical testing | The p.Q217* pathogenic mutation (also known as c.649C>T), located in coding exon 4 of the FLCN gene, results from a C to T substitution at nucleotide position 649. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This alteration was reported in a cohort of 22 French individuals with Birt-Hogg-Dube syndrome in an individual with skin findings including fibrofolliculomas, epidermoid cysts and acrochordons; multiple lung cysts; a Bosniak renal cyst; and nodules and cysts in the thyroid (Kluger N et al. Br. J. Dermatol., 2010 Mar;162:527-37). In addition to the information 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. |
Invitae | RCV003500542 | SCV004297084 | pathogenic | Birt-Hogg-Dube syndrome | 2023-07-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 449402). This premature translational stop signal has been observed in individual(s) with clinical features of Birt-Hogg-Dubé syndrome (PMID: 19785621, 29357828). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln217*) 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). |