ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1021del (p.Arg341fs) (rs1060502368)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470306 SCV000549436 pathogenic Multiple fibrofolliculomas 2020-08-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg341Glyfs*12) 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 with symptoms of Birt-Hogg-Dube syndrome (PMID: 15852235, Invitae). This variant is also known as c.1473delC in the literature. ClinVar contains an entry for this variant (Variation ID: 409378). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000485342 SCV000565008 pathogenic not provided 2021-02-22 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); This variant is associated with the following publications: (PMID: 29357828, 21937013, 19802896, 15852235)
Ambry Genetics RCV000492409 SCV000580751 pathogenic Hereditary cancer-predisposing syndrome 2017-08-10 criteria provided, single submitter clinical testing The c.1021delC pathogenic mutation, located in coding exon 6 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1021, causing a translational frameshift with a predicted alternate stop codon (p.R341Gfs*12). This mutation (designated as c.1473delC) was reported in a patient with multiple fibrofolliculomas (Schmidt LS et al. Am. J. Hum. Genet., 2005 Jun;76:1023-33). 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.

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