Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000082619 | SCV000114661 | pathogenic | not provided | 2013-07-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000165348 | SCV000216072 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-06 | criteria provided, single submitter | clinical testing | The p.Q373* pathogenic mutation (also known as c.1117C>T), located in coding exon 7 of the FLCN gene, results from a C to T substitution at nucleotide position 1117. This changes the amino acid from a glutamine to a stop codon within coding exon 7. This mutation has been described in a 47-year-old woman with pulmonary cysts, recurrent pneumothoraces, cutaneous fibrofolliculomas, and a family history of multiple affected relatives (Rehman HU. Can. Respir. J. 19(3):193-5). 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. |
Gene |
RCV000082619 | SCV000321660 | pathogenic | not provided | 2018-03-27 | criteria provided, single submitter | clinical testing | This variant is denoted FLCN c.1117C>T at the cDNA level and p.Gln373Ter (Q373X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one family with Birt-Hogg-Dub? syndrome (Rehman 2012) and is considered pathogenic. |
Invitae | RCV000635546 | SCV000756962 | pathogenic | Birt-Hogg-Dube syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln373*) 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 (BHDS) (PMID: 22679611). ClinVar contains an entry for this variant (Variation ID: 96469). For these reasons, this variant has been classified as Pathogenic. |