ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1513G>A (p.Val505Ile) (rs376715412)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475725 SCV000549434 uncertain significance Multiple fibrofolliculomas 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 505 of the FLCN protein (p.Val505Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs376715412, ExAC 0.02%). This variant has not been reported in the literature in individuals with FLCN-related disease. ClinVar contains an entry for this variant (Variation ID: 409376). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV000572433 SCV000673453 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-05 criteria provided, single submitter clinical testing Insufficient or conflicting evidence

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