ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1300G>A (p.Glu434Lys)

dbSNP: rs1266098984
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001036172 SCV001199523 uncertain significance Birt-Hogg-Dube syndrome 2023-01-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 434 of the FLCN protein (p.Glu434Lys). This variant also falls at the last nucleotide of exon 11, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Birt-Hogg-Dubé_syndrome (PMID: 18234728, 19785621, 25519458). ClinVar contains an entry for this variant (Variation ID: 835319). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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