ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1176+1G>C

dbSNP: rs1555607929
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002038045 SCV002269243 likely pathogenic Birt-Hogg-Dube syndrome 2021-07-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This sequence change affects a donor splice site in intron 10 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 (ExAC no frequency). 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.
Ambry Genetics RCV002331569 SCV002632286 likely pathogenic Hereditary cancer-predisposing syndrome 2020-04-17 criteria provided, single submitter clinical testing The c.1176+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 7 of the FLCN gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. 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 likely pathogenic.
GeneDx RCV003442987 SCV004170513 pathogenic not provided 2023-10-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD)

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