ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.584del (p.Gly195fs) (rs878855217)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230881 SCV000291448 pathogenic Multiple fibrofolliculomas 2020-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly195Glufs*28) 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 several individuals affected with Birt-Hogg-Dubé syndrome (PMID: 15852235, 18234728). This variant is also known as c.1036delG and c.1039delG in the literature. ClinVar contains an entry for this variant (Variation ID: 241927). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000230881 SCV000298050 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255719 SCV000321655 pathogenic not provided 2020-02-19 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 2016); Also known as c.1036delG and c.1039delG; This variant is associated with the following publications: (PMID: 27734835, 29357828, 19562744, 19802896, 21937013, 15852235, 18234728)
Ambry Genetics RCV000492527 SCV000580726 pathogenic Hereditary cancer-predisposing syndrome 2019-01-11 criteria provided, single submitter clinical testing The c.584delG pathogenic mutation, located in coding exon 3 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 584, causing a translational frameshift with a predicted alternate stop codon (p.G195EFS*28). This mutation has been reported in multiple unrelated individuals with a clinical diagnosis of Birt-Hogg-Dube (BHD) syndrome (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun;76:1023-33; Toro JR et al. J. Med. Genet. 2008 Jun;45:321-31; Rossing M et al. J Hum Genet. 2017 Feb;62(2):151-157). Of note, this alteration is also designated as c.1039delG and c.1036delG in 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.
GenomeConnect, ClinGen RCV000230881 SCV000607195 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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