ClinVar Miner

Submissions for variant NM_006070.6(TFG):c.754G>A (p.Gly252Ser) (rs561904697)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821580 SCV000962342 uncertain significance Hereditary motor and sensory neuropathy, Okinawa type; Spastic paraplegia 57, autosomal recessive 2019-03-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 252 of the TFG protein (p.Gly252Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs561904697, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TFG-related disease. 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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