ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1283C>A (p.Pro428His) (rs199889477)

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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 RCV000163906 SCV000214500 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-12 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (benign)
Invitae RCV000529447 SCV000632832 uncertain significance Multiple fibrofolliculomas 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 428 of the FLCN protein (p.Pro428His). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and histidine. This variant is present in population databases (rs199889477, ExAC 0.02%). This variant has not been reported in the literature in individuals with a FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 184619). 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, this variant has uncertain impact on FLCN function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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