ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1418T>C (p.Val473Ala) (rs144883828)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575471 SCV000673401 likely benign Hereditary cancer-predisposing syndrome 2017-02-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other data supporting benign classification
GeneDx RCV000609939 SCV000728987 likely benign not specified 2018-02-13 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.
Invitae RCV000460964 SCV000549452 uncertain significance Multiple fibrofolliculomas 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 473 of the FLCN protein (p.Val473Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs144883828, 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: 409388). 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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