ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.514A>G (p.Ile172Val)

dbSNP: rs1290646710
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689969 SCV000817642 uncertain significance Birt-Hogg-Dube syndrome 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 172 of the FLCN protein (p.Ile172Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 569359). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002334279 SCV002644811 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-29 criteria provided, single submitter clinical testing The p.I172V variant (also known as c.514A>G), located in coding exon 3 of the FLCN gene, results from an A to G substitution at nucleotide position 514. The isoleucine at codon 172 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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