ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.1345A>G (p.Met449Val)

gnomAD frequency: 0.00003  dbSNP: rs767686554
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001069258 SCV001234413 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 449 of the PLEKHG5 protein (p.Met449Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs767686554, ExAC 0.07%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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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