ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.134C>A (p.Ala45Glu)

dbSNP: rs556510460
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791768 SCV000931030 uncertain significance Birt-Hogg-Dube syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 45 of the FLCN protein (p.Ala45Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid. 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. 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. This variant has not been reported in the literature in individuals with FLCN-related disease. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001011021 SCV001171298 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-23 criteria provided, single submitter clinical testing The p.A45E variant (also known as c.134C>A), located in coding exon 1 of the FLCN gene, results from a C to A substitution at nucleotide position 134. The alanine at codon 45 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is not 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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