ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.296del (p.Asp99fs) (rs398124534)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000082634 SCV000114676 pathogenic not provided 2012-12-26 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239648 SCV000298042 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000082634 SCV000321652 pathogenic not provided 2021-02-15 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 19802896, 18234728, 21937013, 23757202, 29357828, 15852235)
Ambry Genetics RCV000492350 SCV000580757 pathogenic Hereditary cancer-predisposing syndrome 2018-03-22 criteria provided, single submitter clinical testing The c.296delA pathogenic mutation, located in coding exon 2 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 296, causing a translational frameshift with a predicted alternate stop codon (p.D99Vfs*31). This alteration was previously described in two unrelated families with Birt-Hogg-Dube syndrome, one of which had two family members with fibrofolliculomas and lung cysts, and one of which consisted of an individual with fibrofolliculomas, renal tumors, lung cysts, and multiple pneumothoraces (Toro JR, J. Med. Genet. 2008 Jun; 45(6):321-31; Schmidt LS, Am. J. Hum. Genet. 2005 Jun; 76(6):1023-33). Of note, this alteration is also designated as c.751delA in the published literature. 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.
Invitae RCV000239648 SCV000940601 pathogenic Multiple fibrofolliculomas 2020-08-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp99Valfs*31) 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 Birt-Hogg-Dubé syndrome (PMID: 15852235, 18234728). This variant is also known as c.751delA in the literature. ClinVar contains an entry for this variant (Variation ID: 96482). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV000239648 SCV000606962 not provided Multiple fibrofolliculomas no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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