ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.235_238del (p.Ser79fs) (rs750146811)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222354 SCV000278166 pathogenic Hereditary cancer-predisposing syndrome 2019-02-19 criteria provided, single submitter clinical testing The c.235_238delTCGG pathogenic mutation (also known as c.733delTCGG) located in coding exon 1 of the FLCN gene, results from a deletion of 4 nucleotides between positions 235 and 238, causing a translational frameshift with a predicted alternate stop codon (p.S79Tfs*50). This mutation was first reported as strongly segregating with an isolated primary spontaneous pneumothorax (PSP) phenotype in a large Finnish family (Painter JN et al. Am. J. Hum. Genet. 2005; 76:522-7). 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 RCV000239626 SCV000298039 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000255605 SCV000321649 pathogenic not provided 2020-04-03 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 at a significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 27780965, 29357828, 24430303, 19116017, 23223565, 15657874, 19802896, 21937013, 19562744)
Invitae RCV000239626 SCV001387569 pathogenic Multiple fibrofolliculomas 2020-07-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser79Thrfs*50) in the FLCN gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with bullous lung lesions and pneumothorax in a family (PMID: 15657874). ClinVar contains an entry for this variant (Variation ID: 3371). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000255605 SCV001449557 pathogenic not provided 2014-05-28 criteria provided, single submitter clinical testing
OMIM RCV000003538 SCV000023696 pathogenic Pneumothorax, primary spontaneous 2009-09-01 no assertion criteria provided literature only

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