Submissions for variant NM_144997.7(FLCN):c.1305del (p.Phe435fs)

dbSNP: rs398124527

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082627	SCV000114669	pathogenic	not provided	2013-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492221	SCV000580719	pathogenic	Hereditary cancer-predisposing syndrome	2017-11-21	criteria provided, single submitter	clinical testing	The c.1305delT pathogenic mutation, located in coding exon 9 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 1305, causing a translational frameshift with a predicted alternate stop codon (p.P435Lfs*33). This mutation has been described in a patient with Birt–Hogg–Dube syndrome (BHD) who had a personal history of fibrofolliculoma, renal tumor, lung cyst, and pneumothorax, and no family history of BHD (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun; 76(6):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.
Invitae	RCV000703847	SCV000832771	pathogenic	Birt-Hogg-Dube syndrome	2024-01-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe435Leufs*33) 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 syndrome (PMID: 15852235). This variant is also known as c.1758delT. ClinVar contains an entry for this variant (Variation ID: 96475). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000082627	SCV002585624	pathogenic	not provided	2023-05-01	criteria provided, single submitter	clinical testing	FLCN: PVS1, PM2
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000703847	SCV003806429	pathogenic	Birt-Hogg-Dube syndrome	2023-03-02	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000703847	SCV004188174	pathogenic	Birt-Hogg-Dube syndrome	2023-07-07	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.