ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.592G>A (p.Asp198Asn) (rs200168437)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569608 SCV000673420 benign Hereditary cancer-predisposing syndrome 2017-02-13 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Other data supporting benign classification
GeneDx RCV000121103 SCV000530066 likely benign not specified 2018-01-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ITMI RCV000121103 SCV000085271 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000341795 SCV000401015 uncertain significance Spontaneous pneumothorax 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000228569 SCV000401016 uncertain significance Multiple fibrofolliculomas 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000228569 SCV000291450 uncertain significance Multiple fibrofolliculomas 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 198 of the FLCN protein (p.Asp198Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200168437, ExAC 0.02%), 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: 134426). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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