ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.250-1G>A (rs786202081)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164717 SCV000215388 pathogenic Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing The c.250-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 2 of the FLCN gene. This pathogenic mutation, designated as IVS4-1G>A, has been previously reported in a Birt-Hogg-Dube family (Schmidt LS et al. Am. J. Hum. Genet. 2005 Jun; 76(6):1023-33). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239714 SCV000298041 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000490144 SCV000576551 pathogenic not provided 2017-04-28 criteria provided, single submitter clinical testing The c.250-1G>A variant in the FLCN gene has previously been reported in at least one family with Birt-Hogg-Dube syndrome (Schmidt et al., 2005). This variant destroys the canonical splice acceptor site in intron 4, and is expected to cause abnormal gene splicing resulting in an in-frame protein product with an abnormal message. However, in the absence of RNA/functional studies, the actual effect of c.250-1G>A is unknown. Based on the currently available evidence, we consider c.250-1G>A to be pathogenic.

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