ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1117C>T (p.Gln373Ter) (rs398124524)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000082619 SCV000114661 pathogenic not provided 2013-07-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV000165348 SCV000216072 pathogenic Hereditary cancer-predisposing syndrome 2019-03-28 criteria provided, single submitter clinical testing ​<span style="background-color:initial">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.
GeneDx 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 Multiple fibrofolliculomas 2020-02-07 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Birt-Hogg-Dubé syndrome (BHDS) (PMID: 22679611). ClinVar contains an entry for this variant (Variation ID: 96469). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.

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