ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.499C>T (p.Gln167Ter) (rs587782069)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130556 SCV000185426 pathogenic Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing The p.Q167* pathogenic mutation (also known as c.499C>T), located in coding exon 3 of the FLCN gene, results from a C to T substitution at nucleotide position 499. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This mutation has been identified in multiple individuals with Birt-Hogg-Dube syndrome (Menko FH et al. Fam. Cancer. 2013 Sep;12:373-9; Luijten MN et al. Hum. Mol. Genet. 2013 Nov;22:4383-97; Johannesma PC et al. Fam. Cancer. 2016 Apr;15:297-300; Demir M and ÇobanoÄŸlu N. Pediatr. Pulmonol. 2016 Jun 3. doi: 10.1002/ppul.23496. [Epub ahead of print]). 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239654 SCV000298048 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255173 SCV000321654 pathogenic not provided 2015-06-04 criteria provided, single submitter clinical testing The Q167X nonsense variant in the FLCN gene has been reported previously in association with Birt-Hogg-Dube syndrome (BHD) (Luijten et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000239654 SCV000632875 pathogenic Multiple fibrofolliculomas 2020-03-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln167*) 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 individuals affected with clinical features of Birt-Hogg-Dubé syndrome, in at least one of whom it was found de novo (PMID: 27652079, 23784378, 26603437, 27257988, 23264078). ClinVar contains an entry for this variant (Variation ID: 141865). 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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