ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.247G>A (p.Glu83Lys)

gnomAD frequency: 0.00001  dbSNP: rs757060348
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000421206 SCV000532954 uncertain significance not provided 2023-03-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000540761 SCV000632864 uncertain significance Birt-Hogg-Dube syndrome 2023-12-08 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 83 of the FLCN protein (p.Glu83Lys). This variant is present in population databases (rs757060348, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 390184). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV000563799 SCV000673439 likely benign Hereditary cancer-predisposing syndrome 2016-10-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences RCV003409606 SCV004116283 uncertain significance FLCN-related condition 2023-10-11 criteria provided, single submitter clinical testing The FLCN c.247G>A variant is predicted to result in the amino acid substitution p.Glu83Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-17131205-C-T). It has conflicting interpretations of likely benign and uncertain significance (https://preview.ncbi.nlm.nih.gov/clinvar/variation/390184/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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