Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479064 | SCV000566978 | pathogenic | not provided | 2015-06-19 | criteria provided, single submitter | clinical testing | The c.1300+2 T>G splice site variant in the FLCN gene destroys the canonical splicedonor site in intron 11. It is predicted to cause abnormal gene splicing, either leading to anabnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormalprotein product if the message is used for protein translation. Although this variant hasnot been previously reported to our knowledge, we consider it to be pathogenic. |
Labcorp Genetics |
RCV005090932 | SCV005765944 | likely pathogenic | Birt-Hogg-Dube syndrome | 2024-09-03 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 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–Dube ́ syndrome (PMID: 20618353, 37490463). ClinVar contains an entry for this variant (Variation ID: 419280). 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. |