ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1219del (p.Ser407fs)

dbSNP: rs878855213
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228856 SCV000291427 pathogenic Birt-Hogg-Dube syndrome 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser407Alafs*61) in the FLCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Birt-Hogg-Dubé (BHD) syndrome (PMID: 27642565). ClinVar contains an entry for this variant (Variation ID: 241915). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000255255 SCV000321663 pathogenic not provided 2021-04-09 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); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Burkett 2016); This variant is associated with the following publications: (PMID: 27642565)
Ambry Genetics RCV003165654 SCV003860942 pathogenic Hereditary cancer-predisposing syndrome 2022-11-02 criteria provided, single submitter clinical testing The c.1219delA pathogenic mutation, located in coding exon 8 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1219, causing a translational frameshift with a predicted alternate stop codon (p.S407Afs*61). This alteration was detected in an individual with multiple, bilateral lung cysts and numerous spontaneous pneumothoraces, as well as a sister with multiple pneumothoraces (Burkett A et al. Respir Med Case Rep. 2016 Aug;19:106-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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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