ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1430G>A (p.Arg477Gln) (rs748878853)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000379332 SCV000400984 uncertain significance Spontaneous pneumothorax 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000266163 SCV000400985 uncertain significance Multiple fibrofolliculomas 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000414396 SCV000491087 uncertain significance not provided 2018-01-20 criteria provided, single submitter clinical testing This variant is denoted FLCN c.1430G>A at the cDNA level, p.Arg477Gln (R477Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FLCN Arg477Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the C-terminus that interacts with FNIP1 and FNIP2 (Baba 2006). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FLCN Arg477Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000266163 SCV000632842 uncertain significance Multiple fibrofolliculomas 2019-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 477 of the FLCN protein (p.Arg477Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs748878853, ExAC 0.006%). This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 322061). 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.
Fulgent Genetics,Fulgent Genetics RCV000765332 SCV000896595 uncertain significance Multiple fibrofolliculomas; Pneumothorax, primary spontaneous; Potocki-Lupski syndrome; Carcinoma of colon; Renal cell carcinoma, nonpapillary 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011546 SCV001171879 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-08 criteria provided, single submitter clinical testing Insufficient or conflicting evidence

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