ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.779G>A (p.Trp260Ter)

dbSNP: rs368778627
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000635567 SCV000756985 pathogenic Birt-Hogg-Dube syndrome 2023-07-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp260*) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 161246). This premature translational stop signal has been observed in individuals with Birt-Hogg-Dubé syndrome (PMID: 18579543, 22068306). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs368778627, gnomAD 0.0009%).
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000635567 SCV002073130 pathogenic Birt-Hogg-Dube syndrome criteria provided, single submitter clinical testing The stop gained p.W260* in FLCN (NM_144997.7) has been reported previously in families with Birt-Hogg-Dube syndrome (Frohlich BA et al; Sattler EC et al). The variant has been submitted to ClinVar as Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Pathogenic
Ambry Genetics RCV002408655 SCV002673291 pathogenic Hereditary cancer-predisposing syndrome 2023-08-10 criteria provided, single submitter clinical testing The p.W260* pathogenic mutation (also known as c.779G>A), located in coding exon 4 of the FLCN gene, results from a G to A substitution at nucleotide position 779. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This variant has been shown to co-segregate with disease in two families in the literature (Fröhlich BA et al. Eur. Respir. J., 2008 Nov;32:1316-20; Sattler EC et al. Acta Derm. Venereol., 2012 Mar;92:187-8). 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.
Myriad Genetics, Inc. RCV000635567 SCV003806642 pathogenic Birt-Hogg-Dube syndrome 2023-01-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
CSER _CC_NCGL, University of Washington RCV000148502 SCV000190213 pathogenic Familial spontaneous pneumothorax 2014-06-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.