Submissions for variant NM_144997.7(FLCN):c.396+1G>A

dbSNP: rs2145009900

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002049690	SCV002313316	likely pathogenic	Birt-Hogg-Dube syndrome	2021-11-06	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 5 of the FLCN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of Birt-Hogg-Dubé syndrome (PMID: 24393238). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003321897	SCV004026720	likely pathogenic	not provided	2025-03-04	criteria provided, single submitter	clinical testing
Division of Respiratory Medicine of Juntendo University, Juntendo University Faculty of Medicine and Graduate School of Medicine	RCV002049690	SCV004032384	pathogenic	Birt-Hogg-Dube syndrome	2023-07-01	no assertion criteria provided	clinical testing