ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1201C>T (p.Arg401Cys) (rs143183215)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492247 SCV000580716 likely benign Hereditary cancer-predisposing syndrome 2017-03-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae RCV000233961 SCV000291426 uncertain significance Multiple fibrofolliculomas 2018-05-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 401 of the FLCN protein (p.Arg401Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs143183215, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 241914). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). 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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